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The use of intracytoplasmic sperm injection has increased substantially worldwide, primarily in couples with non-male factor infertility. However, there is a paucity of evidence from randomised trials supporting this approach compared with conventional in-vitro fertilisation (IVF). We aimed to investigate whether intracytoplasmic sperm injection would result in a higher livebirth rate compared with conventional IVF. This open-label, multicentre, randomised trial was done at two IVF centres in Ho Chi Minh City, Vietnam (IVFMD, My Duc Hospital and IVFAS, An Sinh Hospital). Eligible couples were aged at least 18 years and the male partner's sperm count and motility (progressive motility) were normal based on WHO 2010 criteria. Couples had to have undergone two or fewer previous conventional IVF or intracytoplasmic sperm injection attempts, have used an antagonist protocol for ovarian stimulation, and agree to have two or fewer embryos transferred. Couples were randomly assigned (1:1) to undergo either intracytoplasmic sperm injection or conventional IVF, using block randomisation with variable block size of 2, 4, or 8 and a telephone-based central randomisation method. The computer-generated randomisation list was prepared by an independent statistician who had no other involvement in the study. Embryologists and couples were not masked to study groups because of the type of interventions and differences in hospital fees, but clinicians performing embryo transfer were unaware of study group allocation. The primary outcome was livebirth after the first embryo transfer from the initiated cycle. Analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT03428919. Between March 16, 2018, and Aug 12, 2019, we randomly assigned 1064 couples to intracytoplasmic sperm injection (n=532) or conventional IVF (n=532). Livebirth after the first embryo transfer from the initiated cycle occurred in 184 (35%) of 532 couples randomly assigned to intracytoplasmic sperm injection and in 166 (31%) of 532 couples randomly assigned to conventional IVF (absolute difference 3·4%, 95% CI −2·4 to 9·2; risk ratio [RR] 1·11, 95% CI 0·93 to 1·32; p=0·27). 29 (5%) couples in the intracytoplasmic sperm injection group and 34 (6%) couples in the conventional IVF group had fertilisation failure (absolute difference −0·9%, −4·0 to 2·1, RR 0·85, 95% CI 0·53 to 1·38; p=0·60). In couples with infertility in whom the male partner has a normal total sperm count and motility, intracytoplasmic sperm injection did not improve the livebirth rate compared with conventional IVF. Our results challenge the value of the routine use of intracytoplasmic sperm injection in assisted reproduction techniques for this population. My Duc Hospital and Merck Sharp and Dohme.

Background It has been well documented that the maturing oocyte is very vulnerable to changes in its micro-environment, the follicular fluid (FF). Recent research has focused on different components within this FF, like hormones, growth factors and metabolites, and how their concentrations are altered by diet and the metabolic health of the mother. It has been proposed that fatty acids (FAs) are potential factors that influence oocyte maturation and subsequent embryo development. However, a thorough study of the specific FF FA composition per lipid fraction and how this may be affected by BMI is currently lacking. Therefore, we investigated the BMI-related concentration of FAs in the phospholipid (PL), cholesteryl-ester (CHE), triglyceride (TG) and non-esterified (NE) lipid fraction in the FF of women undergoing assisted reproductive treatment (ART). Methods In this descriptive cross-sectional study, the FF of normal weight (18.5 ≤ BMI < 25.0 kg/m(2), n = 10), overweight (25.0 ≤ BMI < 30.0 kg/m(2), n = 10) and obese (BMI ≥ 30.0 kg/m(2), n = 10) women, undergoing ART, was sampled and analyzed for 23 specific FAs in the PL, CHE, TG and NEFA fraction, using a gas chromatographic analysis method. Differences between BMI-groups were studied by means of univariate general linear models and post hoc Sheffé tests. Results Total FA concentrations in the PL and CHE fraction did not differ between BMI groups. Total TG concentrations tended to differ and total NEFA concentrations differed significantly between BMI groups. Interestingly, 42% and 34% of the total FAs was esterified in the PL and CHE fraction, respectively, while only 10% were present in both the TG and NEFA fraction. Only few individual FA concentrations differed in the PL, CHE and TG fraction between BMI groups, whereas abundant BMI-related differences were found in the NEFA fraction. Conclusions Our data show that differences in BMI are associated with alterations in the FA composition of the FF, an effect most pronounced in the NEFA fraction. These BMI-related variations could possibly affect granulosa cell viability, oocyte developmental competence and subsequent embryo quality possibly explaining differences in oocyte quality in obese patients described by others.

Background Assisted Reproductive Technology (ART) has undergone considerable changes over the last decade, with consequences on ART outcomes in different regions of the world being unknown. Methods We conducted a systematic review of published national and regional ART registry data to assess how changes in clinical practice between 2004 and 2013 have impacted outcomes in Australia and New Zealand, Canada, Continental Europe, the United Kingdom (U.K.), Japan, Latin America, and the United States (U.S.). The data reflect 7,079,145 total ART cycles utilizing both fresh and previously cryopreserved embryos from autologous oocytes that resulted in 1,454,724 live births. This review focused on the following measures: ART cycle volume, use of cryopreserved embryos, single embryo transfer (SET), live birth rates in fresh and frozen-thawed cycles, and perinatal outcomes in recent years. Results SETs and utilization of frozen-thawed embryos increased worldwide over the study period. In 2012 SET utilization in all ART cycles was highest in Japan and Australia/New Zealand (82.6% and 76.3% respectively) and lowest in Latin America (16.0%). While gradual improvements in live birth rates were observed in most regions, some demonstrated declines. By 2012–2013, fresh cycle live birth rates were highest in the U.S. (29%) and lowest in Japan (5%). In Japan, the observed decline in fresh cycle live birth rate coincided with transition to minimal stimulation protocols, transfer of frozen-thawed rather than fresh embryos, and implementation of an SET policy. Similarly, implementation of an SET policy in parts of Canada was followed by a decline in fresh cycle live birth rate. Increasing live birth rates in frozen-thawed embryo cycles, seen all over the world, partially compensated for declines in fresh ART cycles. During 2012–2013 Australia/New Zealand and Japan reported the lowest multiple delivery rates of 5.6 and 4% respectively while the US had the highest of 27%. In recent years, preterm delivery rates in all regions ranged between 9.0 to 16.6% for singletons, 53.9 to 67.3% for twins, and 91.4 to 100% for triplets and higher order multiples. Inconsistencies in the way perinatal outcome data are presented by various registries, made comparison between regions difficult. Conclusions ART practices are characterized by outcome differences between regions. International consensus on the definition of ART success, which accounts for perinatal outcomes, may help to standardize worldwide ART practice and improve outcomes. Trial registration PROSPERO ( CRD42016033011 )

Sixteen artificial intelligence (AI) and machine learning (ML) approaches were reported at the 2018 annual congresses of the American Society for Reproductive Biology (9) and European Society for Human Reproduction and Embryology (7). Nearly every aspect of patient care was investigated, including sperm morphology, sperm identification, identification of empty or oocyte containing follicles, predicting embryo cell stages, predicting blastocyst formation from oocytes, assessing human blastocyst quality, predicting live birth from blastocysts, improving embryo selection, and for developing optimal IVF stimulation protocols. This represents a substantial increase in reports over 2017, where just one abstract each was reported at ASRM (AI) and ESHRE (ML). Our analysis reveals wide variability in how AI and ML methods are described (from not at all or very generic to fully describing the architectural framework) and large variability on accepted dataset sizes (from just 3 patients with 16 follicles in the smallest dataset to 661,060 images of 11,898 human embryos in one of the largest). AI and ML are clearly burgeoning methodologies in human reproduction and embryology and would benefit from early application of reporting standards.

Sperm cryopreservation has been widely used in assisted reproductive technology (ART) and has resulted in millions of live births. Two principal approaches have been adopted: conventional (slow) freezing and vitrification. As a traditional technique, slow freezing has been successfully employed and widely used at ART clinics whereas the latter, a process to solidify liquid into an amorphous or glassy state, may become a faster alternative method of sperm cryopreservation with significant benefits in regard to simple equipment and applicability to fertility centers. Sperm vitrification has its own limitations. Firstly, small volume of load is usually plunged to liquid nitrogen to achieve high cooling rate, which makes large volume sample cryopreservation less feasible. Secondly, direct contact with liquid nitrogen increases the potential risk of contamination. Recently, new carriers have been developed to facilitate improved control over the volume and speed, and new strategies have been implemented to minimize the contamination risk. In summary, although sperm vitrification has not yet been applied in routine sperm cryopreservation, its potential as a standard procedure is growing.

Recent decades have seen declining total fertility rates (TFR) globally, alongside increased use of assisted reproductive technology (ART). However, TFR includes ART births and excludes induced abortions, complicating assessments of population fecundity. Here, we examine trends in cohort total fertility rates (cTFR), induced abortions, and ART use through a nationwide cohort study of 1,648,971 pregnancies, including abortions, among Danish women aged 15–45 years born between 1958 and 1999. A new index, the Comprehensive Unassisted Pregnancy Rate (live births and induced abortions, excluding ART births), was developed. Our findings reveal a decline in unassisted pregnancy rates for women born after 1961, with an accelerated decline for those born after 1970. In contrast, cTFR increased for women born between 1958 and 1970 before decreasing, driven by trends in induced abortions and ART births. These differences highlight a disconnect between cTFR and fecundity measures. The declining unassisted pregnancy rates, reduced abortions, and increased ART demand raise concerns about population fecundity. Understanding these trends’ biological and socioeconomic drivers requires large-scale, transdisciplinary studies of representative populations. Our results emphasize the need for alternative measures, like the Comprehensive Unassisted Pregnancy Rate, to assess reproductive health and fertility trends accurately.

This comprehensive review explores the evolving landscape of sperm selection techniques within the realm of Assisted Reproductive Technology (ART). Our analysis delves into a range of methods from traditional approaches like density gradient centrifugation to advanced techniques such as Magnetic-Activated Cell Sorting (MACS) and Intracytoplasmic Morphologically Selected Sperm Injection (IMSI). We critically assess the efficacy of these methods in terms of sperm motility, morphology, DNA integrity, and other functional attributes, providing a detailed comparison of their clinical outcomes. We highlight the transition from conventional sperm selection methods, which primarily focus on physical characteristics, to more sophisticated techniques that offer a comprehensive evaluation of sperm molecular properties. This shift not only promises enhanced prediction of fertilization success but also has significant implications for improving embryo quality and increasing the chances of live birth. By synthesizing various studies and research papers, we present an in-depth analysis of the predictability of different sperm selection procedures in ART. The review also discusses the clinical applicability of these methods, emphasizing their potential in shaping the future of assisted reproduction. Our findings suggest that the integration of advanced sperm selection strategies in ART could lead to more cost-effective treatments with reduced duration and higher success rates. This review aims to provide clinicians and researchers in reproductive medicine with comprehensive insights into the current state and future prospects of sperm selection technologies in ART.

Background Online interest could serve as critical sentinel indicators for monitoring assisted reproductive technology (ART) demands, detecting regions with access inequities, and identifying shortcomings in policy frameworks; however, global online interest of ART has not been assessed. The study aims to investigate the spatiotemporal evolution of online interest in ART globally. Methods The study follows retrospective observational design. Data were derived from Google Trends and Relative Search Volume (RSV) data across 230 countries and regions were collected. After quality control, data from 59, 76, 69, and 61 countries and regions were included for different search terms (“Assisted reproductive technology,” “In vitro fertilization,” “Intracytoplasmic sperm injection,” and “Preimplantation genetic diagnosis,” respectively). Weekly percentage changes (WPCs) and annual percentage changes (APCs) were used to quantify the temporal variations in online interest. Results Globally, public online interest in ART demonstrated a distinct seasonal fluctuation, peaking during months 3–5 and 9–11, while declining in months 6–8 and 12 − 2. The global online interest showed a significant downward trend (APC = -11.22%, 95% Confidence Interval [CI]: -18.44 to -8.61) from 2004 to 2011, followed by a gradual increase from 2011 to 2016 (APC = 1.76%, 95% CI: -7.64 to 11.99). Interest then rapidly increased from 2016 to 2019 (APC = 27.24%, 95% CI: 12.48 to 35.20), before continuing to decline after 2020 (APC = -6.54%, 95% CI: -12.52 to -3.05) with predictions indicating further decreases by 2030. Overall, Europe exhibited relatively higher online interest, while Africa and Oceania showed lower levels. In Europe, France (RSV = 76), Italy (RSV = 66), and Spain (RSV = 32) had notable interest in ART. Whereas, in Oceania and Africa, Australia (RSV = 8), New Zealand (RSV = 6), Tunisia (RSV = 16), Algeria (RSV = 16), and Nigeria (RSV = 10) showed lower levels of interest. Israel, Réunion (France), and France ranked as the top three countries or regions with the highest online interest in ART worldwide. Conclusions Global online interest in ART shows significant variation across countries and regions, with a decline after 2020. To address these trends, ART resources and services should be allocated effectively based on seasonal and regional demand. Government action is needed to raise social awareness and improve the accessibility and utilization of ART.

This analysis of data from the U.S. National Center for Health Statistics and the CDC showed a decline in triplet and higher-order births between 1998 and 2011 that coincided with a reduction in the transfer of three or more embryos during in vitro fertilization. In vitro fertilization (IVF) and non-IVF fertility treatments (i.e., ovulation induction and ovarian stimulation) constitute major risk factors for the genesis of multiple births (twin, triplet, and higher-order births). 1 IVF procedures, which are defined as procedures in which eggs and sperm are manipulated with the purpose of establishing a pregnancy, represent the overwhelming majority of procedures for assisted reproductive technology. Ovulation induction and ovarian stimulation, which are often included as part of the IVF process, are also coupled with timed intercourse or intrauterine insemination to establish a pregnancy independently of IVF. In ovulation induction, drugs are administered to induce ovulation . . .

Purpose This study aims to summarize and analyze the existing research on anxiety and depression within the field of assisted reproduction technology, exploring current hotspots, emerging frontiers, and trends, while offering insights for future research directions. Methods Relevant literature on anxiety and depression among assisted reproduction patients was retrieved from the Web of Science Core Collection up to December 31, 2023. The analysis, encompassing studies, countries, authors, institutions, keywords, and co-citation networks, was visualized using VOSviewer version 1.6.19 and the “bibliometrix” R package version 4.3.1. Results A total of 1458 studies were included in the analysis. The literature on anxiety and depression in assisted reproduction patients has shown a fluctuating upward trend. Human Reproduction was identified as the leading journal, with the highest citations across multiple journals. Boivin J emerged as the most prolific author, with Cardiff University contributing the most publications. The USA and China led in terms of both publications and citations. Highly cited studies were predominantly published between 1995 and 2007, with half of the included studies published before 2000. Key research hotspots included evidence synthesis, acupuncture treatment for infertility, and the mental health of patients undergoing assisted reproductive technology, particularly focusing on anxiety and depression. Conclusion As awareness of psychological health in assisted reproductive technology continues to grow, future research should focus on mitigating anxiety and depression to enhance patient outcomes and patient quality of life. Integrating psychological support and monitoring long-term psychological outcomes are crucial for optimizing assisted reproductive technology success and fostering holistic, patient-centered care.