Background: Cryopreservation of oocytes is central to assisted reproductive technologies (ART) and fertility preservation. Conventional vitrification (CVT), though widely used, involves prolonged exposure to high concentrations of cryoprotective agents (CPAs), potentially inducing cellular stress. Ultrafast freeze–thaw (UFFT) aims to minimize CPA exposure and achieve extreme cooling/warming rates, reducing cryodamage. Objective: To compare UFFT and CVT in mouse oocytes, focusing on spindle/polar body morphology, necrosis percentage via PI⁺ extracellular vesicles (EVs), and mitochondrial unfolded protein response (mtUPR) activation. Methods: Metaphase II oocytes (n = 100/group) were assigned to fresh control, CVT, or UFFT groups. Post-thaw morphology was assessed via light/polarized microscopy; necrosis was quantified as PI⁺ EV fraction by flow cytometry; mtUPR activation (Hsp60, Lonp1, Atf5, ClpP) was measured by qRT-PCR. Data were analyzed by ANOVA with Tukey’s post-hoc test. Results: UFFT oocytes exhibited significantly higher spindle integrity (91% ± 3%) and polar body retention (94% ± 3%) than CVT (65% ± 5% and 70% ± 4%, respectively; p < 0.001). PI⁺ EV percentage was reduced in UFFT (18.0% ± 3.0%) compared to CVT (34.0% ± 4.0%; p < 0.001). mtUPR gene expression was highest in CVT, intermediate in UFFT, and lowest in the fresh control. Differences between UFFT and control were not statistically significant (p > 0.05). Conclusion: UFFT preserved oocyte morphology and reduced membrane damage compared to CVT, without significantly elevating mitochondrial stress markers above control. These findings support UFFT as a promising alternative in ART, warranting further large-scale and clinical studies.
Purpose. Conventional IVF laboratory key performance indicators (KPIs) are reported as single (“sole”) ratios in which the denominator excludes mature oocytes lost to the procedure. We tested whether the blastocyst utilization rate overstates true performance by masking post-ICSI oocyte degeneration, and we developed two complementary corrections that put degeneration back into the denominator. Methods. Retrospective analysis of a single pooled ICSI cohort of 7,216 cycles and 56,349 MII oocytes. Against the conventional blastocyst utilization rate (BUR = Frozen/2PN), we defined: a Degeneration-Penalized BUR (DP-BUR) that adds the degenerated oocytes back to the denominator — additive, Frozen/(2PN + ATR), and multiplicative, (Frozen/2PN) × (1 − ATR/MII) — and a True BUR (TBUR = Frozen/MII) anchored to all mature oocytes. Degeneration was stratified at < 5% versus ≥ 5%. We assessed each metric against a competence benchmark of 40% (blastocysts utilization rate) and quantified operator-level misclassification (operators anonymized). Results. Conventional BUR was 41.9; DP-BUR was 40.2 (additive) and 40.5 (multiplicative); TBUR was 32.8 — bracketing the correction, with DP-BUR attributing the gap to degeneration alone (+ 4% over the true value) and TBUR to all mature-oocyte attrition (+ 28%). The corrections were degeneration-dependent and, for DP-BUR, degeneration-specific: from < 5% to ≥ 5% degeneration, DP-BUR fell from 54.4% to 42.7% while conventional BUR barely moved (54.6%→52.0%), so DP-BUR is essentially flat where degeneration is low and drops only where it is high; TBUR fell 46.1%→38.4%. Against a benchmark of 40%, conventional BUR passed 24 of 38 operators, DP-BUR passed 17 (7 flipped from pass to fail), and TBUR passed 7 (17 flipped). Two cycles with identical mature-oocyte and fertilization counts but different degeneration are scored identically by both conventional BUR and TBUR, and are separated only by DP-BUR. Conclusions. Conventional blastocyst utilization overstates true performance in proportion to the degeneration it hides. A degeneration-penalized denominator (DP-BUR) isolates operator-induced oocyte damage, while an MII-anchored denominator (TBUR) reports true yield from biological starting material; both pass operators and laboratories that an honest accounting would fail.
Embryologists operate in highly demanding environments where burnout is an increasingly recognized occupational hazard. This review aims to delineate the types, causes, and consequences of burnout among embryologists, compare burnout prevalence across medical laboratory specialties, and propose evidence-based strategies for mitigation, emphasizing its impact on patient outcomes and laboratory performance. A comprehensive literature review synthesized findings from cross-sectional surveys, meta-analyses, systematic reviews, and consensus guidelines related to burnout in healthcare and laboratory settings. Special focus was given to embryology-specific data, including occupational stressors, emotional labor, and workload metrics. Comparative analyses were performed to contextualize embryologist burnout within broader laboratory medicine. Embryologists report the highest emotional burnout levels among assisted reproductive technology (ART) professionals. Contributing factors include excessive workloads, irregular hours, outcome visibility, ethical dilemmas, limited career progression, and poor interdepartmental communication. Burnout negatively affects cognitive performance, psychomotor precision, protocol adherence, and communication, directly impacting IVF outcomes. High-burnout laboratories show increased witnessing discrepancies and reduced patient satisfaction. Evidence suggests that burnout is not only a personnel issue but also a critical quality and safety concern. Burnout in IVF laboratories is a systemic issue that compromises embryologist well-being and ART success. Multilevel interventions—spanning organizational policies, regulatory frameworks, leadership development, and technological innovations—are essential. Integrating burnout assessment into routine quality assurance and regulatory monitoring can enhance staff sustainability and patient care outcomes in reproductive medicine.
PURPOSE OF REVIEW:This study aimed to examine if excess body weight impacts the outcomes of IVF treatment cycles. RECENT FINDINGS:While data on the effect and/or association of excess weight on IVF outcomes continue to produce mixed results, recent studies stratifying analyses by age are yielding clarity on a detrimental potential of obesity on IVF outcomes. Specifically, IVF outcomes in the third decade of life are susceptible to adverse implications of excess weight, as reflected in lower clinical pregnancy and live birth rates. Plausible pathogenic mechanisms underlying the detrimental impact of excess weight on IVF outcomes include inflammation, DNA repair, insulin resistance, and the targets of such mechanisms that include the spectrum of players critical to reproductive success, including the oocyte, sperm, embryo, and uterine receptivity. SUMMARY:The detrimental implications of excess weight on IVF outcomes are more pronounced by age, and inflammatory processes seem to be particularly relevant to the interplay of weight excess, adiposity, and IVF cycle outcomes.
Mitochondria is an important organelle for the oocyte-to-embryo transition in the early embryonic development period. The oocyte uses mitochondria functionally and its mitochondrial DNA (mtDNA) content as the main energy source in the embryo development at the preimplantation stage. The aim of this study is to compare mitophagic, apoptotic and humanin gene expressions from the culture medium fluid in which embryos are developed and monitored among normoresponder (NOR), polycystic ovary syndrome (PCOS), young and older patients with poor ovarian reserve (POR). The study groups consisted of infertile patients who applied to the Bahçeci Umut IVF Center as NOR (Control), PCOS, POR-Advanced (POR-A) and POR-Young (POR-Y). After the isolation of total RNA from the collected samples, MFN1, MFN2, PINK1, PARKIN, SMN1, SMN2, p53 and Humanin gene expressions were determined by Real Time-PCR. The average age of only the POR-A was determined to be higher than the NOR (p < 0.001). The MFN1, SMN2 (p < 0.05), Humanin and p53 gene expressions (p < 0.001) increased, while PINK1 gene expression decreased (p < 0.05), in the POR-Y compared to the NOR. A decrease in MFN2, PARKIN (p < 0.05) and PINK1 gene expressions was determined in the PCOS compared to the NOR (p < 0.001). Furthermore, a decrease was observed in MFN2, PINK1 (p < 0.001) and Humanin gene expressions compared to the NOR (p < 0.05). The current data are the first in the literature determining the apoptotic and mitophagic status of the oocyte. The current results prove that waste embryo culture fluid may provide a non-invasive profile for important cellular parameters such as mitochondrial dysfunction in female infertility. The evaluation of significant cellular parameters can be performed much earlier without any intervention into the embryo.
We analyze the psychological and interpersonal aspects of in vitro fertilization (IVF) laboratory operations, highlighting how human factors such as leadership style, emotional intelligence (EI), and team dynamics influence the effectiveness of IVF treatments. We also examine the role of personality dynamics in team functioning and the adverse effects of toxic behaviors on laboratory performance and morale. The manuscript comprehensively reviews contemporary literature about leadership styles, EI, and team dynamics. It also includes a detailed analysis of the ramifications of their operations within IVF laboratories. The primary emphasis resides in determining how these human factors contribute to the overall efficacy of IVF treatments and following patient outcomes. The findings suggest that staff well-being is not just a concern, but a critical factor in enhancing successful IVF outcomes. Leadership styles that promote emotional intelligence and healthy team dynamics significantly improve laboratory performance. On the other hand, a toxic workplace negatively impacts staff well-being and patient outcomes. The study highlights the need for management development and EI training as vital components of successful IVF laboratory operations, reassuring the audience that these measures can lead to improved outcomes. This manuscript presents the case for an equitable operational framework that recognizes the value of soft skills and technical expertise in IVF laboratories. It underscores the significance of emphasizing the human element in reproductive medicine, proposing that by prioritizing empathy and delineating the contributions of the human factor, the field can achieve its maximum potential and enhance outcomes for staff members and patients. The pivotal role of future research in empirically substantiating the influence of these human factors in realizing successful IVF laboratories cannot be overstated, and we urge the academic community to participate actively in this crucial area of research.
Objective: Gonadotropin-releasing hormone agonist (GnRHa) trigger induces both Luteinizing hormone (LH) and follicle stimulating hormone (FSH) surges, impacting oocyte maturation, and mitochondrial dysfunction, is responsible for chromosomal anomalies during meiotic divisions. This study aimed to investigate the effect of GnRHa instead of human chorionic gonadotropin (hCG) triggers on unfolded protein responses against embryonic stress in oocytes and embryos. Materials and Methods: Female mice were divided into control, hCG-triggered, and GnRHa-triggered groups. Superovulation was performed. Oocytes were retrieved 13h after hCG or GnRHa injection, and two pronuclei (2PN) oocytes were retrieved 24h after the appearance of a vaginal plug. ATF5, GRP78, and HSP60 protein levels were analyzed by Western blot. One-way ANOVA and Students' t-test were used for statistical analysis. Results: When comparing the GnRHa group to the hCG group, their respective oocyte maturation rates (79.8% vs. 75.9%), oocyte areas (10198 mu m2 and 9474 mu m2), 2PN rates (78% vs. 72%), and blastocyst formation rates (82% vs. 77%) were significantly higher (p < 0.05). The HSP60 protein level was significantly lower in the GnRHa group compared to the hCG group (22% vs. 55%, p < 0.05). Additionally, the ATF5 protein level was significantly lower in the hCG group compared to the GnRHa group (p < 0.0001). Conclusion: GnRHa trigger improves oocyte nuclear and cytoplasmic maturation, as well as blastocyst formation rates. The underlying mechanism for this effect is the downregulation of HSP60 and upregulation of ATF5 levels.
Incorporating artificial intelligence (AI) into in vitro fertilization (IVF) laboratories signifies a significant advancement in reproductive medicine. AI technologies, such as neural networks, deep learning, and machine learning, promise to enhance quality control (QC) and quality assurance (QA) through increased accuracy, consistency, and operational efficiency. This comprehensive review examines the effects of AI on IVF laboratories, focusing on its role in automating processes such as embryo and sperm selection, optimizing clinical outcomes, and reducing human error. AI’s data analysis and pattern recognition capabilities offer valuable predictive insights, enhancing personalized treatment plans and increasing success rates in fertility treatments. However, integrating AI also brings ethical, regulatory, and societal challenges, including concerns about data security, algorithmic bias, and the human–machine interface in clinical decision-making. Through an in-depth examination of current case studies, advancements, and future directions, this manuscript highlights how AI can revolutionize IVF by standardizing processes, improving patient outcomes, and advancing the precision of reproductive medicine. It underscores the necessity of ongoing research and ethical oversight to ensure fair and transparent applications in this sensitive field, assuring the responsible use of AI in reproductive medicine.
As interest in deep space travel grows exponentially, understanding human adaptation in becoming an interplanetary species is crucial. This includes the prospect of reproduction. This review summarizes recent updates and innovations in assisted reproductive technologies (ART) on Earth, while also discussing current challenges and areas for improvement in adapting ART studies to the space environment. We discuss the critical components of ART - gamete handling and preparation, fertilization, embryo culture, and cryopreservation - from the daily practice perspective of clinical embryologists and reproductive endocrinologists and lay out the complicated path ahead. In vitro embryo development in low Earth orbit and beyond remains questionable due to synergetic effects of microgravity and radiation-induced damage observed in simulated and actual in-space mammalian studies. Cryopreservation and long-term storage of frozen samples face substantial obstacles - temperature limitations, lack of trained personnel, and absence of adapted cosmic engineering options. We touch on recent innovations, which may offer potential solutions, such as microfluidic devices and automated systems. Lastly, we stress the necessity for intensive studies and the importance of an interdisciplinary approach to address numerous practical challenges in advancing reproductive medicine in space, with possible implications for both space exploration and terrestrial fertility treatments.
As the space industry grows exponentially and aspirations for space travel expand, we are entering a new era where we will very likely become an interplanetary species. Although reproduction is an essential human function and necessary for species survival, we have remarkably little knowledge regarding the impact of space travel on the female reproductive system. The effects of spaceflight on human reproductive potential, fertility, implantation and subsequent pregnancy resulting in a healthy live birth must be considered before planning prolonged spaceflight missions and the colonization of planets. In this review, we explore what is known and what remains to be learned about the effects of space travel on female reproductive endocrinology. We also delve deeper into reproductive endocrinology and discuss normal physiologic mechanisms at the molecular level to have a better understanding of how it may change during spaceflight. The rigors of spaceflight including radiation, gravitational stressors, and circadian rhythm changes could potentially affect ovulation, fertilization, endometrial receptivity, preimplantation embryo development, embryo implantation, placentation, and pregnancy. Thus, we will examine what is known about spaceflight effects on the hypothalamic–pituitary–gonadal (HPG) axis, ovarian folliculogenesis and steroidogenesis, early embryogenesis, endometrial receptivity, and pregnancy. We further discuss the recent advances in reproductive endocrinology and future research platforms. Establishing a better understanding of the effect of space travel on female reproductive health, as well as developing countermeasures to mitigate adverse effects, are decisive components of our species’ successful transition to an interplanetary one.
The purpose of this review is to address the critical need for standardization and clarity in the use of key performance indicators (KPIs) within the realm of in vitro fertilization (IVF), particularly emphasizing the integration of preimplantation genetic testing (PGT) processes. This review is timely and relevant given the persistently modest success rates of IVF treatments, which stand at approximately 30%, and the growing complexity of IVF procedures, including PGT practices. The review synthesizes recent findings across studies focusing on technical and clinical KPIs in embryology and genetic laboratories, identifying gaps in current research and practice, particularly the lack of standardized KPIs and terminology. Recent findings highlighted include the critical evaluation of technical KPIs such as Intracytoplasmic Sperm Injection (ICSI) fertilization rates, embryo development rates, and laboratory performance metrics, alongside clinical KPIs like the proportion of mature oocytes and clinical pregnancy rates. Notably, the review uncovers a significant gap in integrating and standardizing KPIs for PGT applications, which is essential for improving IVF outcomes and genetic diagnostic accuracy. The implications of these findings are profound for both clinical practice and research. For clinical practice, establishing a standardized set of KPIs, especially for PGT, could significantly enhance the success rates of IVF treatments by providing clearer benchmarks for quality and performance. For research, this review underscores the necessity for further studies to close the identified gaps, promoting a more integrated and standardized approach to KPIs in IVF and PGT processes. This comprehensive approach will not only aid in improving clinical outcomes but also in advancing the field of reproductive medicine.
The SARS-CoV 2 pandemic is now responsible for over 48 million infections and one million deaths worldwide. Pandemics impact population growth not only by excessive mortality, but also by preventing births. In previous pandemics occurring in the 20th and 21st centuries, a trend towards birth rate reduction was observed 9 months later (Figure 1). After the 1918-20 HIN1 influenza pandemic, birth rates dropped by 5 to 15% in comparison to average rates before the pandemic [1]. This drop was related to higher death rates in pregnant patients (case fatality rate of 27%), as well as miscarriages and stillbirths (increased by 0.4% and 2.2% respectively as compared to prior average rates) [1,2]. A rebound in birth rates, however, occurred 1-2 years after this decline [3]. Moreover, several studies have shown that children born in 1919, and thus exposed to the H1N1 virus in utero, experienced worse health and socioeconomic outcomes in older ages than surrounding birth cohorts [4]. SARS-CoV and Ebola were also associated with similar trends in birth rates during and after the pandemics in 2004 and 2015, respectively. In Brazil, the Zika virus pandemic led to a 10 to 20% drop in birth rates [5].
Technologic advances and modern medicine are now reshaping fertility preservation approaches. Introduction of vitrification technique and increased public awareness have created considerable improvements in oocyte cryopreservation programs and have made this option widely offered and used worldwide. In this sense, oocyte quality evaluation has become extremely important and valuable to predict the feasibility as well as the possible outcome of oocyte cryopreservation for future fertility preservation. In this work, we aim at summarizing the current state of oocyte quality evaluation and cryopreservation.
Preimplantation Genetic Testing (PGT) has been performed worldwide since 1990 to reveal the sex of the embryos. Until 2010, blastomere biopsy and Fluorescent In Situ Hybridization (FISH) were standard; however, in 2012, trophectoderm biopsy became predominant.
Embryologist burnout is an under-discussed issue with significant implications for In Vitro Fertilization (IVF) success rates. This manuscript aims to shed light on the challenges faced by embryologists and their potential impact on the clinical outcomes of assisted reproductive technology. By addressing the factors contributing to burnout, we aim to highlight the importance of addressing mental health and work-life balance in reproductive medicine, ultimately leading to improved success rates in IVF.
Objectives: We aimed to investigate a non-invasive selection method to predict competent embryos before frozen-thawed embryo transfer.