Embryology Laboratory Research Articles

P-294 The impact of audit in embryology laboratory and its outcome - A multicentric study

Abstract Study question Would establishing an audit division in the embryology department of a well-organized multicentric IVF chain improve compliance thereby improving laboratory Key Performing Indicators (KPIs)? Summary answer The internal audits not only helped in increasing compliance but also KPIs like blastocyst rate, good blastocyst rate and β-HCG rate across various centers. What is known already Audit plays an important role in multiple industries worldwide. It has been proven to improve compliance with system, process and productivity of the organization. It helps an organization accomplish its objectives by using a systematic, disciplined approach to evaluate and improve the effectiveness of risk management, control and governance processes. As every organization has its own set of SOPs and KPIs there’s no universally accepted audit process; hence we introduced and implemented an indigenously designed audit system to ensure compliance and optimize laboratory performance as per the organizational Standard Operating Protocol (SOPs) to verify the Quality Management System (QMS) implementation. Study design, size, duration A retrospective cohort study was conducted in 30 centers of Indira IVF across India. Audits were planned in 2021/22 and KPIs were compared with pre and post-audit periods. Study duration was April-2019 to March-2022. Various parameters were used to analyze compliance based on checklist of 120 checkpoints divided into 7 categories like facility & lab management, laboratory process, SOP implementation, etc. Audit covered every critical area with 360-degree approach including people, equipment, facility & processes. Participants/materials, setting, methods The compliance rate was considered as the primary outcome and blastocyst, good blastocyst and β-HCG rate were taken as secondary outcomes. Pre-audit (Group-1) and post-audit (GrouP-2) outcomes were compared by paired T-test. The change in compliance rate was calculated as (Average Compliance after 2nd Audit – Average compliance in 1st Audit)/ Average Compliance after 2nd Audit*100. All p < 0.05 were considered statistically significant. Statistical analyses were performed using Statistical Package for social science (IBM SPSS), V28.0. Main results and the role of chance The average percent increase in compliance rate (74.03 ± 7.49 to 80.0 ± 7.94; p < 0.001) was statistically significant. Considering a team of 100 plus embryologists and 175 plus doctors panned across India, this improvement was substantial. The increase in average total blastocyst rate (48.48 ± 15.01 vs 54.52 ± 12.19; p < 0.001), average good blastocyst rate (29.15 ± 9.85 vs 31.05 ± 8.37; p < 0.02) and average β-HCG success rate (71.73 ± 9.97 vs 75.16 ± 8.28; p < 0.001) in G1 and G2 respectively was statistically significant. With respect to 30 individual centers, a statistically significant increase was found in 15 centers for blastocyst rate, in 16 centers for good blastocyst rate and in 7 centers for β-HCG success rate. Leaving 11 centers with blastocyst rate, 7 centers with good blastocyst rate and 17 centers with β-HCG success rates showed improvement though it was non-significant. All audits were carried out by independent competent and qualified auditors. Considering the above-mentioned data, we observed that audit is playing a very vital role in quality management systems. It helps to establish compliance with systems, processes and SOPs thereby improving immediate laboratory KPIs and overall outcomes for even established organizations. Limitations, reasons for caution Due to the Covid-19 pandemic, data from April 2020 to March 2021 could not be collected for analysis. The study has been conducted till β-HCG outcomes. Further, implantation rate and live pregnancy has not been analyzed. Wider implications of the findings “Audit system” plays a very vital role in the IVF laboratory for even SOP-driven organizations to ensure stringent adherence with regards to implementing and ensuring compliance. It is highly recommended that an audit system should be a part of every organization to improve QMS and overall outcomes. Trial registration number not applicable

P-158 Effect of women body mass index on in vitro embryos development and effectiveness of «Assisted reproductive technologies»

Abstract Study question Does a woman's body mass index (BMI) affect the development of an embryo in vitro? Summary answer Evaluation of the development of embryos indicates that the overweight affects the development of the embryo and associated with a lower rate of live births. What is known already Excess weight and obesity - as a cause of infertility, occures against the background of existing metabolic disorders. Severe thinness and, like obesity, often lead to violations of the interval and reproductive functions of a woman. An increase in adipose tissue of more than 20% or more leads to dysfunction of the hypothalamic-pituitary-ovarian system. With obesity and emaciation of the body, a woman has various forms of menstrual disorders, the frequency of uterine bleeding and also endometrial pathology increases. Study design, size, duration This study included the retrospective analysis of Assisted Reproductive Technologies (ART) cycles using statistical data on the development of embryos in the Embryological laboratory, pregnancy and childbirth was carried out from 2016 to 2018. Morphological studies were carried out using Time-Lapse embryo imaging. Participants/materials, setting, methods In this study, morphological and biostatistical methods were used. The cohort of patients aged 20 to 45 years was divided into four groups: 1623 embryos from 243 underweight women; 19542 embryos from 2270 normal weight women (control group); 9701 embryos from 1069 overweight women; and 2668 embryos from 343 obese women. Main results and the role of chance In the group of underweight women the pregnancy rate is 46%, which is 3% less than in overweight and obese group of women, while the percentage of the control group is 47.5%. However, the results of live births in group of women with obesity is 7% less than in women of normal weight, which is 29 and 36 percent respectively. In addition, a comparative analysis of the number of fertilized eggs showed that at a normal BMI, 6.3 ± 0.4 oocytes were fertilized, while in the group of women with second-degree obesity only 4.2 ± 0.3 oocytes. Based on the results of the T-test, it can be concluded that these indicators have differences with a significance level of less than 0.05. Also, the results obtained indicate differences in the maturity of embryos at the blastocyst stage, where blastocysts of excellent quality matured in the control group of 3.4 ± 0.4 embryos, and in the experimental group with obese women 2.4 ± 0.1 embryos. Furthermore, the frequency of live births showed a relationship between the norm and high BMI. In the control group, the result was 0.7 ± 0.02, while in first-degree obesity, the result was 0.2 ± 0.06. Limitations, reasons for caution The main limitation of this study is a verity of women with different anamnesis, which were not taken into account. The grading of blastocysts is subjected to a human factor. The limitation of the Time-lapse technology is the inability to rotate the embryos making it very difficult to observe. Wider implications of the findings This method needs further investigations about limitations, such as the age of patients, type and heaviness of infertility, existing diseases and previous pregnancies in anamnesis. Trial registration number Not Applicable

P-606 Does trigger timing make a difference in oocyte donation?

Abstract Study question Is there optimal trigger timing in controlled ovarian stimulation (COS) for egg donors for better clinical outcome? Summary answer Different trigger timings may not affect oocyte maturity rate. 35 hour’s trigger may create optional timing for embryology to complete fertilization into a natural concept. What is known already Trigger exposure time is still a debatable clinical issue. Ovulation is triggered by administration of hCG or GnRH agonist, with retrieval taking place between 35th and 38th hour post triggering. There was a tendency to decrease post maturity risk for MII oocytes also early triggering will create optional timing for embryology laboratory for denudation, oocyte vitrification and fertilization process under oocyte cytoplasmic maturity (38 hours post trigger) and natural concept fertilization (till 40 hours post trigger) for better clinical outcome. Study design, size, duration This single center retrospective study included oocyte donors (n = 1289) with different timing of eggs retrieving. They were divided into two groups: group A, with exposure of the medicine trigger for 35 h and group B with timing which was 36 h before egg retrieval. We evaluated the concordance between the follicle-to-oocyte index (FOI), antral follicle count (AFC), number of MII oocytes, maturation rate (MR), utilization rate (UR) and the timing of triggering. Participants/materials, setting, methods The number of donors was 784 and 505 in A and B groups respectively. The mean age of the patients in this study was (SD) 26,2 (3,2) and 26,7 (3,3) years. Cycle characteristics were compared. Data was assessed using the Shapiro-Wilk test for the normality of the distribution of the variables. The association between COS cycle parameters and the differences in COS output was assessed by T-Student (parametric) or U-Mann-Whitney (non-parametric). Main results and the role of chance Donors in groups A and B had a similar mean number of oocytes retrieved (33,50±14,12 vs 30,44±13,00), in groups A and B respectively. The same tendency with no statistical difference was mentioned for values number of MII oocytes (SD): 25,16 (11,73) and 20,50 (10,19), for MR - 81% vs 80% and for AFC: 33,50 (14,18) and 30,44 (13,00) in groups A and B, respectively. Unexpectedly, values for UR and FOI (SD) were statistically significant different (p = <0.05): 94,1% (17,2) vs 89,1% (20,2) and 92,51 (11,43) vs 83,43 (15,63), accordingly, in group A and B respectively. Group A donor oocytes vitrified on 38 hours post trigger and fertilized on 40 hours from sibling oocytes. Group B donor oocytes vitrified on 39 hours and fertilized on 42 hours from sibling oocytes. Values for oocyte survival rate post warming were statistically non-significant different (p > 0.05): 96,64% (10,95) vs 95,08% (10,03). Cleavage arrest rate were statistically significant different; 8,01% vs 28,06% and used blastocysts rate were statistically significant different; 54,67% (5,02) vs 42,36% (4,08). Values for fertilization were statistically non-significant different; (p > 0.05): 98,64% (12,24) vs 97,08% (11.96) and used blastocysts rate were statistically significant different; 67,22% (6,18) vs 51,88%. (5,07) Limitations, reasons for caution This study is limited by its retrospective nature and the established strict time parameters of the study can be considered a limitation. Wider implications of the findings As we can see, the issue of the optimal period for oocyte retrieval after the administration of human chorionic gonadotropin should be considered very individually and in further studies it is possible to take into account wider time intervals in the design of trials. Trial registration number not applicable

Real-time image and time-lapse technology to select the single blastocyst to transfer in assisted reproductive cycles

The success of an assisted reproduction cycle should be the achievement of a healthy singleton live birth following the replacement of one embryo. Therefore, one of the most critical points for embryologists has been the selection criteria and how to choose the best embryo to transfer with high implantation potential. In this vein, morphological evaluation has been historically the method applied. However, this practice relies on a limited number of single observations and is associated with high operator variability. Recently, a major innovation in embryo culture has been the introduction of a new type of incubator with integrated time-lapse monitoring, which enables the embryologist to analyze the dynamic events of embryo development, from fertilization to blastocyst formation. This novel practice is quickly growing and has been implemented in many IVF clinics worldwide. Therefore, the main aim of this review is to illustrate the benefits of time-lapse technology in a modern embryology laboratory. In particular, we discuss the blastocyst collapse(s) event and morphometric blastocyst assessment and analyse their association with embryo viability and implantation potential.

Analysis of the clinical outcomes of microbial contamination caused by environmental contamination of the embryology laboratory during IVF-ET treatment cycles

BackgroundBacterial contamination may cause loss of or damage to cultured oocytes or embryos, resulting in the lack of transplantable embryos during IVF embryo culture. However, there are few reports about IVF embryo contamination caused by embryology laboratories. In this work, we evaluated clinical pregnancy outcomes and the risk of maternal and infant complications after embryo contamination caused by environmental pollution during IVF.MethodsThe authors retrospectively analyzed 2490 IVF-ET ovulation induction therapy cycles in the Reproductive Center of Yichang Central People's Hospital from January 2015 to May 2022. According to the presence or absence of embryo culture medium contamination, the two groups were divided into an embryo contamination cycle and a nonembryo contamination cycle. The primary outcome parameters were the characteristics and progress of embryo culture medium contamination. Embryo laboratory outcomes, pregnancy outcomes, and maternal and infant complications were secondary outcome parameters.ResultsOne case of embryo contamination originated from semen contamination. The remaining 15 cases involved environmental contamination outbreaks in embryo culture chambers, caused by Staphylococcus pasteuri. Compared with conventional uncontaminated IVF cycles, the 15 cases of contaminated embryo cycles showed no significant difference in embryo laboratory outcomes, pregnancy outcomes, or maternal and infant complications except for a slightly higher rate of fetal growth retardation. Ultimately, 11 live-born infants were successfully delivered, of which 2 were premature. The remaining 4 patients did not become pregnant after 1–2 transfers due to a lack of transferable embryos.ConclusionWhen the embryo culture medium is contaminated due to the environmental contamination of the IVF culture room, it is feasible to perform daily rapid rinsing of the culture medium and avoid blastocyst culture as remedial treatment. However, the long-term impact on offspring needs further prospective research.

Education of the clinical embryology laboratory professional: development of a novel program delivered in a laboratory medicine department

Clinical embryologists are responsible for the handling, evaluation, and care of human gametes and preimplantation embryos within the context of an assisted reproductive technology laboratory. They are integral members of a team of professionals who provide care for fertility patients. Despite the increasing recognition of clinical embryologists as professionals, training requirements, continuing professional development, and appropriate credentialing have lagged in several countries. In many cases, individuals enter the profession with training limited to technical aspects provided by individual laboratory directors through an apprenticeship model. In this article, we present the rationale for rigorous formal training in clinical embryology, introduce CanEMB competencies for practicing professional clinical embryologists that are founded on CanMEDs role principles, and present a nascent Masters of Health Sciences degree program in Laboratory Medicine with a specialization in clinical embryology. This 2-year program has unique features including a Clinical Embryology Skills Development Laboratory, research capstone project, and 200-hour placement within a practicing assisted reproductive technology laboratory. Importantly, this program is delivered through a university-based Department of Laboratory Medicine and Pathobiology in partnership with a Department of Obstetrics and Gynecology. Thus, this program represents a formal acceptance of clinical embryology as a clinical laboratory science. It can be adopted elsewhere to provide a relevant, robust education that will meet current and future needs of the profession.

Post-Thaw Day 5 Blastocyst Culture Time Prior to Transfer Does Not Affect Assisted Reproduction Technology (ART) Outcomes in Frozen-Thawed Embryo Transfer Cycles.

The frozen embryo transfer (FET) technique has been progressively used more worldwide due to improved culture conditions, as well as enhanced survival rates after vitrification. However, little is known about the effect of the post-thaw blastocyst culture duration prior to transfer on live birth rate in FET cycles. In this retrospective observational study, we evaluated the influence of two distinct post-thaw blastocyst culture spans (2-4 h versus 20-22 h) on clinical pregnancy and live birth rate. A total of n = 1927 frozen-warmed cycles were included in the analysis. Among those, n = 885 warmed blastocysts were cultured for 2-4 h, and n = 1029 were kept in culture for 20-22 h prior to transfer; the remaining blastocysts did not survive the warming protocol. We observed no significant differences in live birth and clinical pregnancy rates between the two groups. The blastocyst morphological evaluation at transfer improved following the longer culture time. No differences between the two groups were found also for gestational and neonatal outcomes. This work shows that different post-thaw embryo culture timings do not negatively impact pregnancy outcomes. Overall, these results are important in the context of the embryological laboratory in order to better organize the workflow and avoid unnecessary timing-related workload.

Role of Artificial Intelligence in Quality Assurance in ART: A Review

During the last few decades, assisted reproductive technologies (ARTs) have flourished rapidly and accompanied a set of advanced procedures such as intracytoplasmic sperm injection (ICSI), electronic witnessing, digital monitoring through embryoscope time-lapse systems, consistent decision-making algorithms with advanced statistics modes and preimplantation genetic testing (PGT). In usual practice, manual procedures were routinely used in IVF (in vitro fertilization) laboratories worldwide, but automation and artificial intelligence (AI) systems are promising techniques for quality assurance, which reduced the burden on the working staff in the embryology laboratory. In addition, these systems are equipped with powerful mathematical tools that minimize technician variability in the IVF lab and efficiently generate data for impaired gametes and embryos. The principal challenge of single-sperm selection out of 108 gametes can be sorted out by incorporating machine learning algorithms coupled with advanced data processing capabilities. In the same line, the emergence of closed embryo culture systems (CECSs) in human embryology has enabled the accurate morphokinetic evaluation of the more rapid cell division and the identification of normal and abnormal hallmarks of embryo viability. In particular, these CECSs are guided by the latest time-lapse microscopy (TLM) facility to continuously monitor embryo development kinetics without removing them from controlled and stable incubator conditions. In conclusion, AI-driven models can reduce technical variability in sample handling and remove the burden of the most subjective, tedious and/or monotonous aspects of the IVF lab. Furthermore, these systems also highlight environmental stressors that could hamper embryo development competence. In a broader sense, AI-based approaches are more accurate, precise and rapid in predicting embryo quality noninvasively.

2 PRONUCLEI (2PN) BANKING AS A METHOD TO OPTIMIZE COSTS FOR POOR PROGNOSIS PATIENTS DOING MULTIPLE CYCLES WITH PRE-IMPLANTATION GENETIC TESTING FOR ANEUPLOIDY (PGT-A) LEADS TO SIMILAR BLASTOCYST YIELD

With lower ovarian reserve and increased rates of aneuploidy, older patients undergoing in-vitro fertilization (IVF) often need to do multiple cycles to obtain an euploid embryo and may want to bank embryos for future use. This can become prohibitively expensive. In addition, multiple biopsy sessions add significant time and resource allocation in the embryology laboratory. Combining multiple stimulation cycles vitrified at the 2 pronuclei (2PN) stage together to thaw, culture to blastocyst and biopsy as one group may offer a more cost-effective approach.

EMBRYOLOGIST BURNOUT: PHYSICAL AND PSYCHOLOGICAL SYMPTOMS AND OCCUPATIONAL CHALLENGES CURRENTLY REPORTED BY U S EMBRYOLOGISTS

To examine (1) the prevalence of physical and psychological symptoms reported by U.S. embryologists related to their occupation, and how workplace fatigue and burnout may affect their quality of life, professional outlook, efficiency, safety, and attention to detail, (2) to determine how the current workflow and organizational characteristics of the embryology laboratory affect embryologists’ physical and psychological health; and (3) the potential measures that can be taken to improve both working conditions and embryologists’ health and well-being, and patient care.

New cryostorage labware developed for the embryology laboratory significantly reduces temperature changes at ambient conditions compared to traditional cryostorage canes and goblets

Background and Aim: To determine if there is a significant difference in specimen level temperature between new cryostorage labware and traditional canes and goblets when handling through ambient conditions.

Cumulus Cell Analysis for Prediction of Oocyte Quality in IVF and IVM

Background: In order to promote single embryo transfer (SET) in in vitro fertilization (ICSI) and In Vitro Maturation (IVM) supplementary analysis beyond morphological scoring is needed. The symbiosis between oocyte and cumulus during different stages of follicle development suggests the cumulus as an obvious specimen for molecular analysis. Over the last decade several studies have shown the potential of quantitative RT-PCR to measure predictive genes in ART. However, few prospective studies have validated this potential in routine embryology. Aim: Summarize the potential clinical use of cumulus gene testing from studies in routine human IVF and IVM. Methods: Pubmed search and own unpublished data. Results: So far few prospective studies (Adriaenssens et al., 2019; Van Vaerenbergh et al., 2021) have validated the approach for SET on Day 3 in a selected group of IVF (ICSI) patients in an interventional, non-randomized, assessor-blinded cohort study, by using normalized values of three predictive genes. The outcome demonstrated a significant increase in live birth when selecting single day 3 embryo in the first ICSI fresh transfer cycle based on cumulus gene-expression (of transferable embryos) versus SET based on morphology-only (from 27% to 50%; p<0.0001). A similar non-invasive approach could be developed for the decision making in IVM culture-type (depending on GV maturity grade) and to pinpoint the single IVM embryo to transfer. Conclusion: Cumulus analysis proves to be a reliable non-invasive technology with promising applications for the routine embryology laboratory.

Morphological and Skeletal Abnormalities Induced by Rolapitant: An Antiemetic Agent

IntroductionRolapitant hydrochloride is a highly selective, long-acting antagonist of the neurokinin-1 (NK1RA) receptor with a high level of central nervous system (CNS) penetrance. Clinically, it is given to cancer patients with high and moderate emetogenic chemotherapy to prevent chemotherapy-induced nausea and vomiting (CINV). The facts produced in this research support the interpretation of teratogenic effects like anatomical malformations and abnormal skeletal changes affected by high doses of rolapitant in developed chick embryos, which can be extrapolated to humans due to gaps in the literature regarding the teratogenic potential of rolapitant. As rolapitant is metabolized by the liver and excreted through the kidney by leaving a deep impact on the various systems of the body and due to its high plasma concentration with a half-life of more than 180 hours, the study was conducted to acquire some additional information about its adverse effects over the various body systems. Chick is one of the best animals for embryological laboratory research. For various reasons, it is preferred to research embryology in chicks or domestic hens (Gallus domesticus). Chick eggs are large, readily available all year, easy to incubate, and regulate artificially.AimThis study aimed to determine the morphological and skeletal abnormalities due to the effect of rolapitant, an antiemetic agent, in developing White Leghorn (G. domesticus) chicken eggs.Materials and methodsThe experiment used 300 fertilized White Leghorn chicken eggs. The eggs were categorized into five experimental groups (A, B, C, D, and E, each with 30 eggs) and five control groups (a, b, c, d, and e, each with 30 eggs). Rolapitant was administered into the five experimental groups of eggs on incubation day five at various concentrations of 0.00039, 0.0005, 0.00075, 0.001, and 0.00125 mg, respectively, while the control groups received the same volume (0.039, 0.05, 0.075, 0.1, and 0.125 ml, respectively) of normal saline.ResultsAt all doses, the mean weight and crown-rump (CR) length of chick embryos were significantly greater in the control group than in the experimental group. The experimental group died at a higher rate than the control group. Additionally, it was found that the mortality due to the rolapitant dosages increases with dose. All groups except group A showed skeletal anomalies such as poor ossification, bent, and displacement, and morphological abnormalities such as yolk sac retraction, hematoma, and scanty feathers were found in experimental groups C, D, and E. This was shown to be more prevalent in the experimental groups and was exacerbated by subsequent rolapitant dosages.ConclusionRolapitant is toxic when taken in large doses and for an extended period. As a result, rolapitant should be taken only when a valid diagnosis has been established and only at the recommended dose, not at a larger dose or for an extended period of time.

An Update on Non-invasive Approaches for Genetic Testing of the Preimplantation Embryo.

Preimplantation Genetic Testing (PGT) aims to reduce the chance of an affected pregnancy or improve success in an assisted reproduction cycle. Since the first established pregnancies in 1990, methodological approaches have greatly evolved, combined with significant advances in the embryological laboratory. The application of preimplantation testing has expanded, while the accuracy and reliability of monogenic and chromosomal analysis have improved. The procedure traditionally employs an invasive approach to assess the nucleic acid content of embryos. All biopsy procedures require high technical skill, and costly equipment, and may impact both the accuracy of genetic testing and embryo viability. To overcome these limitations, many researchers have focused on the analysis of cell-free DNA (cfDNA) at the preimplantation stage, sampled either from the blastocoel or embryo culture media, to determine the genetic status of the embryo non-invasively. Studies have assessed the origin of cfDNA and its application in non-invasive testing for monogenic disease and chromosomal aneuploidies. Herein, we discuss the state-of-the-art for modern non-invasive embryonic genetic material assessment in the context of PGT. The results are difficult to integrate due to numerous methodological differences between the studies, while further work is required to assess the suitability of cfDNA analysis for clinical application.

IL-6 of follicular fluid and outcome of in vitro fertilization.

The quality of an oocyte is influenced by its microenvironment, which includes cumulus cells and follicular fluid, as well as cells of the immune system and their products. The ovarian interleukins, which are secreted by the granulosa cells and other immune cells within the ovaries and follicles, regulate various functions between the cells. IL-6 is a cytokine that is present in the follicular fluid and may affect the quality of oocytes. There are some inconsistencies in the literature regarding the concentration of interleukin 6 in the follicular fluid.The main objective of this study was to examine whether the concentration of interleukin 6 in the follicular fluid affects the outcome of IVF.This study involved 83 patients who underwent IVF. Follicular fluid was used as the biological material for the analysis. Examination of the obtained follicular fluid and collection of oocytes under a stereomicroscope was performed in the embryological laboratory. The concentration of IL-6 in the follicular fluid was analyzed. IVF and ICSI methods were used as the fertilization methods. Pregnancy was confirmed by the positive serum β-hCG level. The software package SPSS 20 was used for statistical data processing.Analysis of the follicular fluid samples showed a correlation between the concentration of IL-6 in the follicular fluid and the outcome of IVF. The concentration of IL-6 in the follicular fluid was higher in patients with confirmed pregnancy (9.55 ± 7.47 ng/ml).Based on our results, we conclude that the concentration of IL-6 affects the outcome of IVF. If the range of IL-6 concentration is between 3,67 ng/ml and 10 ng/ml, we can expect good IVF outcome with vital pregnancy.

O-082 Patients are requesting to ship their surplus frozen embryos to other countries so that they can be donated to other patients

Abstract Study question Can all patients decide on the destination of their frozen embryos? Summary answer Patients that don’t have the legal right to donate their surplus embryos, still have the opportunity to ship them to centres in Spain What is known already In most European countries the laws do not allow patients to decide on the destination of their surplus vitrified embryos. In Spain, however, all possible options are allowed but certain requirements must be met for each of them: donation, research and destruction. Even though, most couples do not decide on any of them and do not reply to the documents they receive from the Centre. The reasons for this behaviour are not due to an irresponsible attitude but to the fact that it presents them with a difficult situation, which triggers emotional conflicts. Study design, size, duration The goal of this study is to communicate that since 2018 we have received embryo shipment requests from people who have stored their surplus embryos in other countries, where they cannot donate them. We have evaluated 47 cases and accepted 17 from Italy, Belgium, Ireland and Greece. We evaluated the survival rate after thawing and pregnancy rates, and compared them with the results of surplus embryos that have been donated in our Centre. Participants/materials, setting, methods We received applications from patients from different countries. Given the legal difficulties, we only evaluated those from European Community countries. In order to accept the transfer, we require that they meet all the requirements to be “donation eligible”: clinical history and phenotypic features of parents and siblings born from that cycle, serology results prior to treatment, age under 35 years, good embryo morphology score, and all the information from the embryology laboratory of the Centre. Main results and the role of chance According to our Centre's data, only 3% of patients choose to donate their surplus vitrified embryos to others. In a retrospective review of the informed consents of a total of 5,605 IVF cases in which the patients had frozen supernumerary embryos we found that there are no significant differences in this percentage according to the biological origin of the embryos, neither if a couple or a single woman carried out the treatment. Differences are observed between patients from European countries that are close to each other and which are evidence of the idiosyncrasies of each culture. Donation is chosen by 3% of patients from Spain and the UK, 4% from France, 5.5% from Italy, 6% from Germany, 7% from Ireland. We surveyed patients about their reasons for choosing the destination of their embryos: the main reason why they rejected the possibility of donating embryos was the fear that in the future, their children might meet their biological siblings. In these 17 cases that have been shipped from other countries, blastocyst survival rate after thawing was 90% (compared to 97% in donated embryos in our Centre) and pregancy rate was 56% (compared to 59% in our Centre). Limitations, reasons for caution We don’t know the percentage of patients that would agree to donate their cross-border embryos, and most of them are not even aware of this possibility. They concur in a high socio-economic-cultural level that allows them to be informed and if they are accepted, they must pay the shipment fees. Wider implications of the findings We wonder whether all european patients that are interested in donating their embryos and that won’t resign to abandon them should be informed of this possibility. So far, we have had exquisite cooperation from the centres where they remain vitrified. May globalisation allow them to exercise their generosity! Trial registration number Not applicable

EFFICACY OF USING CULTURE MEDIA IN ASSISTED REPRODUCTIVE TECHNOLOGY PROGRAMS

One of the steps to successfully solve the problem of human infertility is the development and improvement of culture media used for the cultivation of embryos in ART programs.  In the past, significant progress has been made in this direction - single-step and two-step culture media have been developed. Both media are widely used in practice to improve the efficiency of individual ART results. The aim of this work was to determine the effectiveness in usage of commercial culture media (Continuous Single Culture Irvine and Origio Sequential Cleav/Blast) in IVF and ICSI programs. A comparative analysis of their impact on embryo quality, fertilization and pregnancy outcomes in IVF and ICSI programs at the Embryology Laboratory of LLP “Centre ECO” in 2017-2021 was conducted. 2650 programs took place, of which 760 programs accounted for IVF and 1890 programs for ICSI. The results of the analysis revealed no significant differences in the use of the above-mentioned media to obtain good quality blastocysts in the IVF program. The usage of the studied culture media showed a higher level of obtaining blastocysts of optimal quality in the ICSI programs when cultured in single-step medium compared to sequential medium. The difference between the two relative values was statistically significant (t=8.08; p0.001). Comparative analysis of the results of embryo cultivation in different nutrient media allow us to conclude that both single-step and sequential culture media, equally contribute to the quality development of blastocysts and demonstrate positive clinical results. Program efficacy based on the factor of ART program ending in pregnancy using CSC Irvine nutrient media was 46.44% for IVF, and 41.42% for ICSI.  Culturing embryos in Origio Sequential Cleav/Blast medium in IVF programs showed pregnancy outcomes at 49.51%, in ICSI programs - 42.85%.

National Canadian Survey on the Management of Noneuploid Embryos

ObjectiveTo comprehensively describe current preimplantation genetic testing for aneuploidy (PGT-A) practices and management of non-euploid embryos in Canada. MethodsThis was a cross-sectional study utilizing an online survey distributed by email to all medical directors of fertility clinics with independent in vitro fertilization (IVF) embryology laboratories. The survey was designed to determine practice patterns regarding PGT-A usage; PGT-A reference laboratory, platform, and thresholds for classifying embryos; and management of embryos classified as mosaic, inconclusive, or aneuploid. ResultsTwenty-five medical directors (69%) participated in the survey. The majority of clinics (91%) offered PGT-A screening, with 45% of clinics offering PGT-A as routine screening. The majority of clinics (90%) that offered PGT-A received mosaicism data; 61% of these clinics had transferred mosaic embryos, and 94% would transfer mosaic embryos. Clinics that performed ≥1000 IVF cycles annually were more likely to have transferred mosaic embryos (100% vs. 45.5%; P = 0.043). The mean percentage of IVF cycles using PGT-A was lower in clinics that had transferred mosaic embryos (12.3% vs. 30.4%; P = 0.033). Only 1 clinic had transferred an aneuploid embryo, but 2 other clinics would consider this option. The majority of clinics (61%) that receive mosaicism data would recommend noninvasive prenatal testing (NIPT) following mosaic embryo transfer, with 22% of clinics indicating that this would be the only genetic test offered. ConclusionWe report significant practice variation in PGT-A and management of non-euploid embryos across Canada and highlight areas where consensus should be encouraged.

A cost-effectiveness analysis of the use of highly purified human menopausal gonadotropins in assisted reproductive technology programs in gonadotropinreleasing hormone agonist or antagonist protocols

Introduction. A comparative analysis of urinary and recombinant gonadotropins is relevant for the enhancement of the effectiveness of assisted reproductive technologies (ART) programs. Of particular interest is the analysis of the pharmacoeconomic efficiency of highly purified human menopausal gonadotropins (HMG) and the identification of individual groups of patients for whom the use of these drugs for ovarian stimulation in the ART program is most feasible and economically justified.Aim. To conduct a cost-effectiveness analysis of the use of Menopur Multidose at a dosage of 1200 IU for ovarian function stimulation in the standard ART protocols with gonadotropin-releasing hormone agonists and antagonists (GnRH-a and GnRH-ant).Materials and methods. The retrospective study included 4080 women aged 20 to 43 years. Stimulation of ovarian function in the ART program was carried out according to the GnRH antagonist protocol in 65.8% of patients and according to the GnRH-a protocol using Menopur Multidose at a dosage of 1200 IU supplemented with Menopur at a dosage of 75 IU used for its indications in 34.2% of women.Results and discussion. The clinical and laboratory data of the patients, stimulated cycle parameters, characteristics of the embryological stage, and the results of the ART program were analysed. The characteristics of the embryological stage met the KPI criteria, reflecting the key performance indicators of the embryology laboratory. Pharmacoeconomic analysis showed high involvement and adherence of patients to the treatment. In addition, it was found that the use of HMG makes efficient use of the budget within the average compulsory health insurance (CHI) tariff and accounts for 12% of the total tariff.Conclusion. Prescription of highly purified HMG (Menopur Multidose 1200 IU) to stimulate ovarian function in patients of different ages is accompanied by an adequate number of mature oocytes, good quality blastocysts, as well as satisfactory indicators of clinical pregnancy. A cost-effectiveness analysis of the use of Menopur Multidose at a dosage of 1200 IU showed that the prescription of this drug is clinically justified and economically feasible in patients of different age groups.

Fertility and Sterility top videos of 2020

To objectively grade all video publications in Fertility and Sterility during 2020 and compile a list of the top 5 surgical videos. Descriptive presentation of the 5 highest scoring video publications from Fertility and Sterility in 2020 SETTING: Not applicable. Not applicable. J.F., Z.K., J.P.P., and S.R.L. acted as independent reviewers of all video publications. A standardized scoring method was used to score all videos. Up to 5 points were awarded for each of the following categories: scientific merit or clinical relevance of the topic, the clarity of the video, the use of innovative surgical technique, and video editing or the use of marking tools on the video to highlight the important features or surgical landmarks. This allowed a maximum score of 20 for each video. The numbers of YouTube views and likes were used as a tiebreaker if ≥2 videos scored similarly. The interclass coefficient from a 2-way random-effects model was calculated to assess for agreement between the 4 independent reviewers. A total of 20 videos were published in Fertility and Sterility during 2020. After averaging scores from all 4 reviewers, a list of top 5 videos was created (Table1). The overall interclass coefficient for the 4 reviews was 0.77 (95% confidence interval, 0.56-0.89). An overall substantial agreement was noted among the 4 reviewers. Five videos particularly stood out within the competitive peer reviewed publications. The subject matter of these videos ranged from complex surgical procedures, including transvaginal natural orifice surgery and advanced endometriosis to basic embryology laboratory topics that covered trophectoderm biopsy and novel intracytoplasmic sperm injection techniques.