A general multi-scale description of metastable adaptive motion across fitness valleys.

We consider a stochastic individual-based model of adaptive dynamics on a finite trait graph G = ( V , E ) . The evolution is driven by a linear birth rate, a density dependent logistic death rate and the possibility of mutations along the directed edges in E. We study the limit of small mutation rates for a simultaneously diverging population size. Closing the gap between Bovier et al. (Ann Appl Probab 29(6):3541-358, 2019) and Coquille et al. (Electron J Probab 26:1-37, 2021) we give a precise description of transitions between evolutionary stable conditions (ESC), where multiple mutations are needed to cross a valley in the fitness landscape. The system shows a metastable behaviour on several divergent time scales, corresponding to the widths of these fitness valleys. We develop the framework of a meta graph that is constituted of ESCs and possible metastable transitions between them. This allows for a concise description of the multi-scale jump chain arising from concatenating several jumps. Finally, for each of the various time scales, we prove the convergence of the population process to a Markov jump process visiting only ESCs of sufficiently high stability.

THE IMPACT OF BIRTH WEIGHT ON INFANT MORTALITY IN KAZAKHSTAN.

INTRODUCTION: Recognizing the importance of birth weight is fundamental to addressing public health challenges associated with maternal and child health. Birth weight serves as a critical indicator, offering insights into mortality, stunting, and the development of chronic diseases later in life. This study delves into fertility and infant mortality trends in Kazakhstan, with a specific focus on understanding urban-rural disparities and gender variations in mortality rates. OBJECTIVES: The primary objective of this study is to evaluate the influence of birth weight on infant mortality in Kazakhstan, considering demographic and regional nuances. Through comprehensive analysis, we aim to discern patterns and factors contributing to infant mortality, thereby informing targeted interventions and policies aimed at improving maternal and child health outcomes across the country. MATERIALS AND METHODS: The analysis was conducted using the data provided by the Republican State Enterprise on the PCV of the "Republican Centre for Electronic Health Care" of the Ministry of Health of Kazakhstan. RESULTS: In Kazakhstan, birth rates reached their zenith in 2021 (total 446,491 births). However, this figure experienced a downturn in 2022, declining to 403,893 births. Notably, urban regions consistently reported higher birth rates compared to rural areas. The year 2022 witnessed a decline in birth rates across both urban and rural populations, with decreases of 9.5% and 11.7%, respectively, compared to the previous year. Analysis using linear regression techniques on infant mortality rates spanning from 2017 to 2022 revealed no statistically significant time trend (slope=51.29, correlation coefficient=0.42, p=0.41). Gender-specific disparities in mortality rates were starkly evident, with boys exhibiting higher mortality rates compared to girls across all population subsets. Geographical analysis conducted in 2022 exposed significant divergences in mortality rates across various regions. CONCLUSIONS: The study highlights significant urban-rural disparities and gender differences in birth rates and infant mortality within Kazakhstan. It also confirms the protective effect of higher birth weight on infant mortality. Regional disparities suggest targeted public health interventions are necessary to address these variations effectively.

A Bayesian Projection of the Total Fertility Rate of Puerto Rico: 2020-2050.

OBJECTIVE: The abrupt decline in the Total Fertility Rate (TFR) of Puerto Rico to 0.9 children per woman, well below the replacement level of 2.1 children per woman, makes the prospect of a sustained population decline a real possibility. Population projections produced by the United States Census Bureau and the United Nations Population Division show that the island population may decline from 3.8 millions in 2000 to slightly above 2 million by 2050, a dramatic population decline of 47% in 50 years. Both population projections assume that all countries with a TFR below replacement level could eventually increase toward or oscillate to 2.1 children per woman and have Puerto Rico's TFR approaching 1.5 by 2050. This assumption has been widely criticized as unrealistic and not supported by evidence. The main objective of our research is to provide an alternative fertility projection for Puerto Rico by 2050 that has more realistic assumptions. METHODS: Our methodology is based on the Bayesian Hierarchical Probabilistic Theory used by the United Nations to incorporate a way to measure the uncertainty and to estimate the projection parameters. We modified the assumptions used by the United Nations by considering 17 countries with TFR similar to Puerto Rico. RESULTS: By 2050, Puerto Rico may have a TFR of 1.1 bounded by a 95% credibility interval (0.56,1.77). CONCLUSION: Under this scenario Puerto Rico can expect to have a larger population decline than that projected by the Census Bureau and the United Nations.

Mortality risk predicts global, local, and individual patterns of human reproduction.

BACKGROUND: Human reproductive dynamics in the post-industrial world are typically explained by economic, technological, and social factors including the prevalence of contraception and increasing numbers of women in higher education and the workforce. These factors have been targeted by multiple world governments as part of family policies, yet those policies have had limited success. The current work adopts a life history perspective from evolutionary biology: like most species, human populations may respond to safer environments marked by lower morbidity and mortality by slowing their reproduction and reducing their number of offspring. We test this association on three levels of analysis using global, local, and individual data from publicly available databases. RESULTS: Data from over 200 world nations, 3,000 U.S. counties and 2,800 individuals confirm an association between human reproductive outcomes and local mortality risk. Lower local mortality risk predicts "slower" reproduction in humans (lower adolescent fertility, lower total fertility rates, later age of childbearing) on all levels of analyses, even while controlling for socioeconomic variables (female employment, education, contraception). CONCLUSIONS: The association between extrinsic mortality risk and reproductive outcomes, suggested by life history theory and previously supported by both animal and human data, is now supported by novel evidence in humans. Social and health policies governing human reproduction, whether they seek to boost or constrain fertility, may benefit from incorporating a focus on mortality risk.

BRP-Net: A discrete-aware network based on attention mechanisms and LSTM for birth rate prediction in prefecture-level cities.

The continuous decline in the birth rate can lead to a series of social and economic problems. Accurately predicting the birth rate of a region will help national and local governments to formulate more scientifically sound development policies. This paper proposes a discrete-aware model BRP-Net based on attention mechanism and LSTM, for effectively predicting the birth rate of prefecture-level cities. BRP-Net is trained using multiple variables related to comprehensive development of prefecture-level cities, covering factors such as economy, education and population structure that can influence the birth rate. Additionally, the comprehensive data of China's prefecture-level cities exhibits strong spatiotemporal specificity. Our model leverages the advantages of attention mechanism to identify the feature correlation and temporal relationships of these multi-variable time series input data. Extensive experimental results demonstrate that the proposed BRP-Net has higher accuracy and better generalization performance compared to other mainstream methods, while being able to adapt to the spatiotemporal specificity of variables between prefecture-level cities. Using BRP-Net to achieve precise and robust prediction estimates of the birth rate in prefecture-level cities can provide more effective decision-making references for local governments to formulate more accurate and reasonable fertility encouragement policies.

Births in the United States, 2023.

Objectives: This report presents 2023 data on U.S. births compared with 2022 and 2021 for several key demographic and maternal and infant characteristics. Methods: Descriptive tabulations of data reported on the birth certificates of the 3.60 million births that occurred in 2023 are presented. Data are presented for the number of births, the general fertility rate, teenage birth rates, the distribution of births by trimester prenatal care began and the distribution of births by selected gestational age categories. Data for 2023 are compared with data for 2022 and 2021. Results: A total of 3,596,017 births were registered in the United States in 2023, down 2% from 2022. The general fertility rate declined 3% in 2023 to 54.5 births per 1,000 females ages 15-44. Birth rates declined for females ages 15-19 (4%), 15-17 (2%), and 18-19 (5%), from 2022 to 2023. The percentage of mothers receiving prenatal care in the first trimester of pregnancy declined 1% to 76.1% in 2023 while the percentage of mothers with no prenatal care increased 5%. The preterm birth rate was essentially unchanged at 10.41% in 2023 but the rate of early term births rose 2%.

Luteinizing hormone supplementation with human menopausal gonadotropin versus low dose human chorionic gonadotropin during ovarian stimulation does not affect live birth rates after fresh and frozen embryo transfer.

AIM: Luteinizing hormone (LH) plays an important role in ovarian follicle maturation. Human menopausal gonadotropin (hMG) or low dose human chorionic gonadotropin (hCG) can provide LH supplementation during in vitro fertilization (IVF) ovarian stimulation, though studies directly comparing their impact on IVF outcomes are limited. The aim of the study was to determine whether LH supplementation with hMG versus low dose hCG during IVF stimulation affects live birth rate. METHODS: Fresh and frozen embryo transfers (ET) from 2017 to 2021 after standard long or antagonist protocols supplemented with hMG (75-250 IU) or low dose hCG (50-100 IU) during stimulation cycles in our academic center were included. Statistical analysis was performed with T-tests, Mann-Whitney U tests, Chi-square, and multiple linear and logistic regression. RESULTS: Four hundred and sixty eight unique stimulation cycles resulting in 213 fresh and 412 frozen embryo transfers were analyzed. There was a lower mature oocyte yield (10.9 vs. 11.8, p = 0.044) but similar high-quality blastocyst yield (3.6 vs. 3.9, p = 0.11) for hMG vs low dose hCG. Live birth rates per transfer were comparable for fresh (42% vs. 49%, p = 0.24) and frozen (46% vs. 53%, p = 0.45) embryo transfers. Multiple logistic regressions showed no association between supplemental gonadotropin and live birth for both fresh and frozen embryo transfers. CONCLUSION: Fresh and frozen IVF-ET pregnancy outcomes were comparable after hMG versus low dose hCG supplementation, suggesting flexibility in supplemental LH dosing regimens that may address patient or physician preference or cost concerns.

Cumulative live birth rate of a blastocyst versus cleavage stage embryo transfer policy during in vitro fertilisation in women with a good prognosis: multicentre randomised controlled trial.

OBJECTIVES: To evaluate whether embryo transfers at blastocyst stage improve the cumulative live birth rate after oocyte retrieval, including both fresh and frozen-thawed transfers, and whether the risk of obstetric and perinatal complications is increased compared with cleavage stage embryo transfers during in vitro fertilisation (IVF) treatment. DESIGN: Multicentre randomised controlled trial. SETTING: 21 hospitals and clinics in the Netherlands, 18 August 2018 to 17 December 2021. PARTICIPANTS: 1202 women with at least four embryos available on day 2 after oocyte retrieval were randomly assigned to either blastocyst stage embryo transfer (n=603) or cleavage stage embryo transfer (n=599). INTERVENTIONS: In the blastocyst group and cleavage group, embryo transfers were performed on day 5 and day 3, respectively, after oocyte retrieval, followed by cryopreservation of surplus embryos. Analysis was on an intention-to-treat basis, with secondary analyses as per protocol. MAIN OUTCOME MEASURES: The primary outcome was the cumulative live birth rate per oocyte retrieval, including results of all frozen-thawed embryo transfers within a year after randomisation. Secondary outcomes included cumulative rates of pregnancy, pregnancy loss, and live birth after fresh embryo transfer, number of embryo transfers needed, number of frozen embryos, and obstetric and perinatal outcomes. RESULTS: The cumulative live birth rate did not differ between the blastocyst group and cleavage group (58.9% (355 of 603) v 58.4% (350 of 599; risk ratio 1.01, 95% confidence interval (CI) 0.84 to 1.22). The blastocyst group showed a higher live birth rate after fresh embryo transfer (1.26, 1.00 to 1.58), lower cumulative pregnancy loss rate (0.68, 0.51 to 0.89), and lower mean number of embryo transfers needed to result in a live birth (1.55 v 1.82; P<0.001). The incidence of moderate preterm birth (32 to <37 weeks) in singletons was higher in the blastocyst group (1.87, 1.05 to 3.34). CONCLUSION: Blastocyst stage embryo transfers resulted in a similar cumulative live birth rate to cleavage stage embryo transfers in women with at least four embryos available during IVF treatment. TRIAL REGISTRATION: International Clinical Trial Registry Platform NTR7034.

Angiogenic factor-driven improvement of refractory thin endometrium with autologous platelet-rich plasma intrauterine infusion in frozen embryo transfer cycles.

Objective: A beneficial effect on endometrial thickness (EMT) and improvement of pregnancy outcome after intrauterine infusion of platelet-rich plasma (PRP) has been suggested. This study assessed the effect of intrauterine PRP infusion on live birth rate and obstetrical outcomes and analyzed cytokines that can potentially improve pregnancy outcomes through PRP. Method: This study was a prospective cohort study conducted in a university hospital fertility center. The study included ninety-one patients who had a history of two or more failed in vitro fertilization (IVF) attempts and refractory thin endometrium that remained unresponsive after at least two conventional treatments for thin endometrium. Patients were treated with an intrauterine infusion of autologous PRP between days 7 and 14 of their hormone replacement therapy-frozen embryo transfer (HRT-FET) cycle. PRP was administered at 3-day intervals until their EMT reached 7mm. After a maximum of three PRP administrations, embryo transfer (ET) was performed. The primary outcome was the live birth rate. Secondary outcomes included the implantation rate and increase in EMT compared to the previous cycle. We compared the cytokines related to angiogenesis in a patient's whole blood (WB) and PRP by utilizing a commercial screening kit. Results: The live birth rate in the PRP treatment cycle was 20.9% (19 of 91 patients), significantly superior to the previous cycle without PRP infusion (p < 0.001). The implantation rate was also significantly higher during the PRP treatment cycle (16.4%) compared to the previous cycle (3.1%) (p < 0.001). The mean EMT post-PRP treatment was 6.1 mm, showing a significant increase of 0.8 mm (p < 0.001). Nonetheless, an increase in EMT was also observed in the non-pregnancy group. No adverse effects were reported by patients treated with autologous PRP. Cytokine array analysis confirmed marked increases in well-known pro-angiogenic factors such as Ang-1, EGF, LAP (TGF-b1), MMP-8, PDGF-AA, and PDGF-AB/PDGF-BB. Conclusion: Intrauterine PRP infusion offers a safe and effective treatment for patients with refractory thin endometrium and implantation failures. The angiogenic cytokines present in PRP are the primary drivers of this improvement.

Two World Wars and Belgium: Missing Births and Birth Sex Ratio Changes.

INTRODUCTION: The sex ratio at birth (male/total births, M/T) is expected to approximate 0.515. M/T is influenced by many factors including stress. Both World Wars have been implicated as influencing birth rates and M/T. This study was carried out to analyse the effects of two World Wars on Belgium vis-à-vis missing births as well as M/T changes. METHODS: Belgian male and female births were available for 1830-2019 and annual population was available from Statista. ARIMA models were used to estimate and project birth losses. The effect of wars was assumed to begin in the years following the commencement of each war and extend to the year after cessation of hostilities i.e., 1915-1919 and 1940-1946 for the First and Second World Wars respectively. RESULTS: This study included 27,346,178 live births for 1830-2019, M/T 0.5124. There was a decreasing trend in births for 1830-2019, significant for 1950-2019. There were dips in births in association with both Wars resulting in over 440,000 missing births, 3.80% of the Belgian population for the First World War and 1.91% for the Second World War. M/T rose non-significantly for the First World War and significantly for the Second World War. DISCUSSION: The declining birth rate and M/T in developed countries is a recognised phenomenon. The missing births in relation to wars are of demographic importance but are often overlooked with emphasis usually on casualties and deaths. M/T may rise in wars, possibly due to increased coital activity as well as other factors.

Neutral effect of Zishen Yutai Pill on frozen-thawed embryo transfer: a propensity score matching study.

Objective: To investigate whether using Zishen Yutai Pills (ZYP) following embryo transfer would affect the live birth rate in frozen-thawed embryo transfer (FET) cycles. Methods: A retrospective analysis was performed on 15044 FET cycles in the Reproductive Medicine Center of The Affiliated Chenggong Hospital of Xiamen University from January 2013 to December 2020. Patients who used Zishen Yutai Pills were defined as Zishen Yutai Pills Group (ZYP, n=2735), while patients who did not use them were defined as Non- Zishen Yutai Pills Group (Non-ZYP, n=12309). The propensity score matching method was used to control for potential confounders between the two groups, and logistic regression analysis was also used to assess whether using ZYP would affect the live birth rate. Results: After propensity score matching, basic characteristics were similar between the two groups. Using ZYP did not increase the pregnancy rate (51.5% vs. 52.7%, P=0.372), and live birth rate (43.0% vs. 44.7%, P=0.354). This was also confirmed by the logistic regression analysis results (OR=0.95, 95%CI=0.85-1.06). In the subgroup analysis of the endometrial preparation protocols, however, it was found that the use of ZYP in patients with natural cycles increased the live birth rate (47.4% vs. 41.5%, P=0.004). A significant interaction between endometrial preparation and ZYP was found (OR=1.38, 95%CI=1.07-1.79) in the multivariate model. Conclusion: The use of ZYP may not improve the live birth rate of unselected patients in FET cycles. However, a future study is needed on the effect of ZYP in natural cycles for endometrial preparation.

GnRH agonist-only trigger, compared to dual trigger, reduces oocyte retrieval rate in high responders without affecting cumulative live birth rate.

Introduction: This study compared, in high responders undergoing IVF treatment, GnRH agonist-only trigger and dual trigger on oocyte retrieval rate and cumulative live birth rate (LBR). The aim was to determine if the GnRH agonist-only triggers had provided outcomes comparable to dual trigger, while minimizing the risk of ovarian hyperstimulation syndrome (OHSS). Materials and methods: A retrospective, matched case-control study was conducted at Taichung Veterans General Hospital, Taiwan, including women who underwent IVF/ICSI between January 1, 2014, and December 31, 2022. Inclusion criteria were: GnRH antagonist protocol and estrogen level >3,000 pg/ml on trigger day. Exclusion criteria were: immune/metabolic diseases, donated oocytes, and mixed stimulation cycles. Propensity score matching was applied to balance age, AMH level, and oocyte number between the GnRH agonist-only and dual trigger groups. Outcomes were analyzed for patients who had complete treatment cycles, focusing on oocyte retrieval rate and cumulative LBR. Results: We analyzed 116 cycles in the agonist-only group, and 232 cycles in the dual trigger group. No inter-group difference was found in their age, BMI, and AMH levels. The dual trigger group had a higher oocyte retrieval rate (93% vs. 80%; p <0.05), while fertilization rates, blastocyst formation rates, and cumulative LBR were comparable. Notably, no OHSS cases had been reported in the GnRH agonist-only group, compared with 7 cases in the dual trigger group. Conclusion: GnRH agonist-only triggers resulted in a lower oocyte retrieval rate compared to dual triggers but did not significantly affect cumulative LBR in high responders. This approach effectively reduces OHSS risk without compromising pregnancy outcomes, making it a preferable option in freeze-all strategies, despite a longer oocyte pick-up duration and a medium cost. GnRH agonist-only trigger, however, may not be suitable for fresh embryo transfers or patients with low serum LH levels on trigger day.

Interrupted time series analysis of the impact of the COVID-19 pandemic and compulsory social health insurance system on fertility rates: a study of live births in Kazakhstan, 2019-2023.

Introduction: The COVID-19 pandemic triggered global health crises, affecting population health directly through infections and fatalities, and indirectly by increasing the burden of chronic diseases due to disrupted healthcare access and altered lifestyle behaviors. Amidst these challenges, concerns regarding reproductive health and fertility rates have emerged, necessitating an understanding of their implications for policymaking and healthcare planning. Furthermore, Kazakhstan's healthcare landscape underwent significant changes with the reintroduction of compulsory social health insurance system in January 2020, coinciding with the onset of the COVID-19 pandemic. This study aims to assess the impact of the COVID-19 pandemic and compulsory social health insurance system on fertility rates in Kazakhstan by examining live birth data from 2019 to 2024. Methods: Using Interrupted Time Series analysis, we evaluated the effect of the COVID-19 lockdown announcement and compulsory social health insurance system implementation on monthly birth rates, adjusted for the number of women of reproductive age from January 2019 to December 2023. Results: In the final model, the coefficients were as follows: the effect of the COVID-19 lockdown was estimated at 469 (SE = 2600, p = 0.8576); the centering variable was estimated at 318 (SE = 222, p = 0.1573), suggesting no significant trend in monthly birth rates over time; the insurance effect was estimated at 7,050 (SE = 2,530, p < 0.01); and the effect of the number of women of reproductive age was estimated at -0.204 (SE = 0.0831, p = 0.01). Discussion: The implementation of the compulsory social health insurance system, rather than the announcement of the COVID-19 lockdown, has had a significant positive impact on live birth rates in Kazakhstan. However, despite governmental efforts, live birth rates are declining, potentially due to unaddressed health needs of fertile women and economic challenges. Urgent policy-level actions are needed to address gaps in healthcare services and promote reproductive health.

The influence of social, demographic and economic factors on fertility trends in Gulf Cooperation Council countries: A longitudinal time trend analysis-1980-2021.

OBJECTIVES: To analyze the fertility rate trends in the GCC countries and their association with socioeconomic factors so that policymakers may use the study findings for future healthcare plans. METHODS: Total population, crude death rate, life expectancy, literacy rate, human development index (HDI), female employment, unemployment rate, urbanisation, gross domestic product (GDP) per capita and inflation were chosen as possible predictors of TFR trends. The data were collected for the Global Burden of Disease 2021 study and other official databases such as the World Bank, the United Nations Development Program and Our World in Data for the 6 Gulf Cooperation Council (GCC) countries. Mean with standard deviation and percentage change was calculated to assess trends of TFR and all other variables from 1980-2021. RESULTS: The fertility rate declined in all 6 countries in 2021 compared to 1980. The highest decline was found in the United Arab Emirates (75.5%), while the lowest was in Kuwait (60.9%). From 1980-2021, total population, life expectancy, HDI, literacy rate, GDP, urbanisation, and female labor force increased in all GCC countries. The total population, life expectancy, urbanisation, female labor force, GDP and HDI were negatively and significantly correlated with TFR (p<0.01). The literacy rate showed a negative and significant correlation with TFR in Bahrain, Kuwait, Saudi Arabia, and Qatar. CONCLUSION: The TFR is declining in GCC countries. The plausible causes include the inclination towards postponement of marriages and excessive costs of living. These trends and associations need to be evaluated by policymakers so that they identify priority areas for interventions, allocate resources and formulate developmental plans accordingly to ensure strategic progress of the region.

Live birth rate after oocyte donation in females diagnosed with turner syndrome: a systematic review and meta-analysis.

BACKGROUND: An enduring challenge for women diagnosed with Turner syndrome (TS) is infertility. Oocyte donation (OD) offers a chance of pregnancy for these patients. However, current data on pregnancy outcomes are inadequate. Hence, this systematic review aims to explore the clinical outcomes of OD in patients with TS. METHODS: A systematic search was conducted in PubMed, Web of Sciences, Scopus, and Embase for relevant papers from 1 January 1990 to 30 November 2023. Our primary research objective is to determine the live birth rate among women with TS who have undergone in vitro fertilization (IVF) using OD for fertility purposes. Specifically, we aim to calculate the pooled live birth rates per patient and per embryo transfer (ET) cycle. For secondary outcomes, we have analyzed the rates of clinical pregnancy achievement per ET cycle and the incidence of gestational hypertensive complications per clinical pregnancy. Prevalence meta-analyses were performed using STATA 18.0 by utilizing a random-effects model and calculating the pooled rates of each outcome using a 95% confidence interval (CI). RESULTS: A total of 14 studies encompassing 417 patients were systematically reviewed. Except for one prospective clinical trial and one prospective cohort study, all other 12 studies had a retrospective cohort design. Our meta-analysis has yielded a pooled live birth rate per patient of 40% (95% CI: 29-51%; 14 studies included) and a pooled live birth rate per ET cycle of 17% (95% CI: 13-20%; 13 studies included). Also, the pooled clinical pregnancy achievement rate per ET cycle was estimated at 31% (95% CI: 25-36%; 12 studies included). Moreover, the pooled rate of pregnancy-induced hypertensive disorders per clinical pregnancy was estimated at 12% (95% CI: 1-31%; 8 studies included). No publication bias was found across all analyses. CONCLUSIONS: This study demonstrated promising pregnancy outcomes for OD in patients with TS. Further studies are essential to address not only the preferred techniques, but also the psychological, ethical, and societal implications of these complex procedures for these vulnerable populations. TRIAL REGISTRATION: This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration code CRD42023494273.

Impact of different progesterone timings on live birth rates for blastocyst frozen embryo transfer cycles.

RESEARCH QUESTION: Do different timings of progesterone administration for day 5 and day 6 blastocysts affect the live birth rate (LBR) of artificial frozen embryo transfer (FET) cycles? DESIGN: This retrospective cohort study included 1362 patients who underwent artificial FET cycles. The effects of 6 and 7 days of progesterone administration prior to blastocyst transfer on clinical outcomes were compared in day 5 and day 6 blastocysts. Univariable and multivariable regression analyses were undertaken. RESULTS: In all patients, LBR was comparable between the two groups (51.8% versus 47.9%, P = 0.165). For day 6 blastocysts, after adjusting for confounders, the 7-day progesterone regimen resulted in a significantly higher LBR (44.8% versus 36.4%, P = 0.039, adjusted OR = 1.494, 95% CI 1.060-2.106) and lower pregnancy loss rate (15.4% versus 25.2%, P = 0.031, adjusted OR = 0.472, 95% CI 0.260-0.856) compared with the 6-day progesterone regimen. For day 5 blastocysts, there were no significant differences in pregnancy outcomes between the two regimens, but the rate of low birthweight was higher with the 7-day progesterone regimen than with the 6-day progesterone regimen (13.9% versus 6.7%, P = 0.032). CONCLUSIONS: In all blastocyst analyses, no difference in LBR was found between the 6- and 7-day progesterone regimens in artificial FET cycles. For day 6 blastocysts, LBR was significantly higher with the 7-day progesterone regimen than with the 6-day progesterone regimen, whereas for day 5 blastocysts, pregnancy outcomes were comparable between the two regimens.

IVF and obstetric outcomes among women of advanced maternal age (≥45 years) using donor eggs.

RESEARCH QUESTION: Does very advanced maternal age (VAMA; age ≥45 years) influence obstetric outcomes among women using donor oocytes in IVF? DESIGN: This retrospective cohort study analysed data from a nationwide IVF registry in Taiwan, focusing on IVF cycles involving women aged 45 years and older using donated oocytes between 2007 and 2016. The study assessed cumulative live birth rates (CLBR) and secondary outcomes such as clinical pregnancy, miscarriage, live birth and twin pregnancy rates, alongside perinatal outcomes such as Caesarean section rates, pre-eclampsia, gestational diabetes and birthweight. RESULTS: The study included 1226 embryo transfer cycles from 745 women, with a stable live birth rate of about 40% across the study period. The CLBR was slightly lower in women aged 50 years and older (54.2%) compared with those aged 45-46 years (58.0%), but these differences were not statistically significant (P = 0.647). Secondary outcomes and perinatal outcomes did not significantly differ across age groups. Regression analysis suggested a non-significant trend towards a decrease in live birth rate and birthweight with increasing maternal age. The study also found that single-embryo transfer (SET) minimized the risk of twin pregnancies without significantly affecting live birth rates. CONCLUSIONS: IVF with donor oocytes remains a viable option for women of VAMA, with consistent live birth rates across age groups. However, the study underscores the importance of elective SET to reduce the risk of twin pregnancies and associated adverse outcomes. Further research is needed to explore the impact of other factors such as paternal age and embryo development stage on IVF success in this population.

The efficacy of diazepam administration during embryo transfer: a retrospective multicenter cohort study on reproductive outcomes.

PURPOSE: This retrospective multicenter cohort study aimed to investigate the impact of diazepam administration during embryo transfer on reproductive outcomes, focusing primarily on the live birth rate. Secondary outcomes included the positive beta-hCG rate, clinical pregnancy rate, miscarriage rate, ectopic pregnancy rate, and preterm birth rate. METHODS: Data from 5607 embryo transfers, encompassing 465 cases with diazepam administration, were retrospectively analyzed. The study included single blastocyst transfers from 12 clinics in Portugal and Spain between January 2015 and December 2022. RESULTS: Comparison of reproductive outcomes between patients receiving diazepam and those who did not showed no statistically significant differences. Positive beta-hCG rates (60.8% non-diazepam vs. 60.4% diazepam, p = 0.92, adjusted p = 0.32) and clinical pregnancy rates (45.6% non-diazepam vs. 46.2% diazepam, p = 0.81, adjusted p = 0.11) were comparable. Miscarriage rates (11.0% diazepam vs. 9.3% non-diazepam, p = 0.25, adjusted p = 0.26) and ectopic pregnancy rates (0.9% diazepam vs. 0.1% non-diazepam, p = 0.1, adjusted p = 0.20) were similar. Live birth rates (36.3% non-diazepam vs. 35.3% diazepam, p = 0.69, adjusted p = 0.82) and prematurity rates (0.3% non-diazepam vs. 0% diazepam, p > 0.99, adjusted p = 0.99) also exhibited no statistically significant differences. CONCLUSIONS: Based on the results, diazepam administration during embryo transfer did not show a discernible impact on reproductive outcomes, including live birth rates, suggesting its limited effectiveness in enhancing success.

Economic evaluation of GnRH-agonist long protocol and GnRH-antagonist protocol in IVT/ICSI among the Chinese population: using pharmacoeconomic models.

OBJECTIVE: This paper uses health economics methods to discuss the cost-effectiveness value of long protocol and antagonist protocol for in vitro fertilisation and embryo transfer (ET) in the Chinese population. DESIGN: Health economic evaluation study. SETTING: The data needed to construct the model for this study were derived from published studies and other secondary sources in China. PARTICIPANTS: No patients participated in the study. MEASURES: The main outcomes were live birth rate (LBR) and cost. From the societal perspective, we considered the direct and indirect costs over the course of the treatment cycles. A cost-effectiveness was measured using the incremental cost-effectiveness ratio and the probability that a protocol has higher net monetary benefit. Sensitivity analysis was carried out to verify the reliability of the simulation results. RESULTS: For the Chinese population, the long protocol resulted in a higher LBR than the antagonist protocol (29.33% vs 20.39%), but at the same time, it was more expensive (ï¿¥29 146.26 (US$4333.17) vs ï¿¥23 343.70 (US$3470.51)), in the case of considering only one fresh ET cycle. It was the same when considering subsequent frozen ET (FET) cycles (51.78% vs 42.81%; ï¿¥30 703.02 (US$4564.62) vs ï¿¥24 740.95 (US$3678.24)). The results of most subgroups were consistent with the results of the basic analysis. However, for certain populations, the long protocol was the inferior protocol (less effective and more expensive). CONCLUSION: For the Chinese population, when the monetary value per live birth was greater than ï¿¥65 420 (US$9726) and ï¿¥66 400 (US$9872), respectively, considering only one fresh cycle and considering subsequent frozen cycles, the long protocol is the preferred protocol. This threshold also varies for women of different ages and ovarian response capacities. For women in POSEIDON (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number) group 2, group 3 and group 4, antagonist protocol is recommended as the preferred protocol. The results of this study need to be verified by further large-scale randomised controlled trials.