Field Of Assisted Reproductive Technology Research Articles

P-382 Clinical case studies of women achieving successful pregnancy outcomes in natural cycle endometrial preparation while continuing breastfeeding: a gap in the existing literature

Abstract Study question Existing research in assisted reproductive technology excludes women who are breastfeeding.The influence of lactation on embryo transfer outcomes remains underexplored. Summary answer This collection of clinical cases underscores the viability of natural cycle endometrial preparation for women who wish to continue breastfeeding while pursuing fertility treatments. What is known already Endometrial preparation for embryo transfer often involves hormonal regimens and synchronization with the menstrual cycle. However, little attention has been given to women who choose to continue breastfeeding while pursuing fertility treatments. This study presents clinical case reports of women who successfully achieved ongoing pregnancies by utilizing natural cycle endometrial preparation during continued lactation, shedding light on a crucial gap in the current literature regarding embryo transfers in lactating women. Study design, size, duration A series of clinical case reports were analyzed, focusing on women who maintained breastfeeding while undergoing natural cycle endometrial preparation for embryo transfer. The cases encompass various age groups and underlying fertility issues. Data collected includes menstrual regularity, hormonal profile, and outcomes of embryo transfers. Participants/materials, setting, methods Retrospective review of a group of women of varying ages and fertility backgrounds who opted to continue breastfeeding while pursuing embryotransfer. We performed frozen embryo transferchoosing natural cycle endometrial preparation. Clinical data were collected from the participants, including menstrual regularity, hormonal assesment, and outcomes of embryo transfers. Patients were monitored to determine the timing of natural ovulation. The women continued breastfeeding throughout their cycle, and embryo transfers were performed according to standard protocols. Main results and the role of chance Our preliminary findings indicate that women who continued breastfeeding during natural cycle endometrial preparation achieved successful pregnancies with evolving embryos. These case reports highlight the potential feasibility of this approach in fertility treatments, despite the limited scientific literature examining the impact of breastfeeding on embryo transfer outcomes. Limitations, reasons for caution Limited number of clinical cases, which may not fully represent the diversity of patient experiences. Additionally, the absence of a control group makes it challenging to draw definitive conclusions about the sole influence of breastfeeding on the outcomes. Future investigations should involve larger cohorts and controlled studies to provide evidence. Wider implications of the findings This collection of clinical cases underscores the viability of natural cycle endometrial preparation for women who wish to continue breastfeeding while pursuing fertility treatments.. These cases advocate for a broader understanding of reproductive options and potential adaptations to existing protocols for lactating women in the field of assisted reproductive technology. Trial registration number not aplicable

O-174 Marginal gains: can small actions in the ART lab improve the environmental impact of medically assisted reproduction?

Abstract Marginal gains can small actions in the ART laboratory improve the environmental impact of medically assisted reproduction? (Invitation) Study question Is it possible to reduce the environmental impact of assisted reproductive technology (ART) laboratories while maintaining quality and safety? Summary answer While individual interventions may yield modest results, their cumulative effect on a wider scale can lead to substantial reductions in resource consumption and emissions over time without compromising treatment outcomes or patient/staff safety. What is known already According to the World Health Organisation (WHO) the change in global climate is one of the gravest threats facing humanity, with pregnant women, new-born and child health considered highly vulnerable. In recent years growing evidence has linked climate change, air pollution, pollutant exposure and microplastics to compromised male and female reproductive health and even spontaneous and in vitro fertilisation (IVF) outcomes. Ironically, the healthcare industry is a major contributor of greenhouse gas emissions, and the rapidly increasing utilisation of ART has raised concerns regarding its environmental footprint. A field primarily driven by highly specialised, energy-intensive laboratory processes, continuous monitoring of hormone testing, single-use consumables and large amounts of waste; the quest for bringing awareness to sustainable practices within ART laboratories is critical, not just for the planet, but for our patients and future generations. Study design, size, duration Alongside a comprehensive review of existing literature, a panel of international professionals and enthusiasts within reproductive medicine, law and environmental science convened in a green conferencing format to discuss key environmental challenges associated with ART and explored potential avenues for enhancing sustainability in the laboratory. A survey and interviews with stakeholders also took place to understand current attitudes and provide real-time social, economic and environmental examples of sustainability in ART laboratories. Main Results I will present a roadmap for sustainability in the IVF laboratory so far. A selection of actions which result in marginal gains within the ART laboratory include but are not limited to: Participate in a ‘green certification’ programme specifically tailored to the IVF laboratory and consider forming a ‘green team’ Aim for energy efficiency, renewable energy, preventive maintenance and consider plug load of non-essential equipment for cost savings. Consider widening operating ranges for temperature and humidity, air circulation changes and HVAC design where possible for energy savings of 15–30% Correct waste management can result in > 30% reduction in clinical waste alongside €11,600 annual savings, with focus on prevention of unnecessary consumables (dishes, media), reducing use of plastics and other single-use items to the extent that is possible and safe, and reusing where appropriate (e.g., training vitrification straws). Adopt electronic platforms for consents/laboratory paperwork; avoiding the use of > 40 pages per cycle in the UK. Reuse packaging materials (cold gel packs, bubble wrap) or form partnerships with local businesses who can reuse. Manage inventory carefully, asking for products with longer expiry dates, and consolidate purchase order to minimise frequency. Minimise liquid nitrogen loss during routine activities and consider batching samples for cryo-transport to minimise frequency of shipments. Limitations Every country, region and laboratory is different and will have their own myriad of regulatory constraints and industry standards to adhere to. This may present barriers to the adoption of certain sustainability measures in ART laboratories and is therefore imperative to seek local guidance first. Wider implications of the findings The carbon footprint of ART extends beyond the laboratory and into the supply chain, encompassing transportation, pharmaceutical production, and waste disposal processes. In this way a holistic approach is necessary, with the need for partnerships between fertility clinics, manufacturers, and regulatory bodies continuously working together to drive the development and adoption of sustainable practices and technologies across the entire ART field.

Monitoring of controlled ovarian stimulation in IVF

Since the inception of in vitro fertilization (IVF), monitoring of controlled ovarian stimulation (COS) has traditionally involved numerous appointments for ultrasound and laboratory testing to guide medication use and dosing, determine trigger timing, and allow for measures to reduce the risk of ovarian hyperstimulation syndrome (OHSS). Recent advances in the field of assisted reproductive technology (ART) have called into question the timing and frequency of COS monitoring appointments, as discussed in this commentary.

Androgens (dehydroepiandrosterone or testosterone) for women undergoing assisted reproduction.

Practitioners in the field of assisted reproductive technology (ART) continually seek alternative or adjunct treatments to improve ART outcomes. This Cochrane review investigates the adjunct use of synthetic versions of two naturally produced hormones, dehydroepiandrosterone (DHEA) and testosterone (T), in assisted reproduction. Steroid hormones are proposed to increase conception rates by positively affecting follicular response to gonadotrophin stimulation. This may lead to a greater oocyte yield and, subsequently, an increased chance of pregnancy. To assess the effectiveness and safety of DHEA and T as pre- or co-treatments in infertile women undergoing assisted reproduction. We searched the following electronic databases up to 8 January 2024: the Gynaecology and Fertility Group (CGF) Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, and trial registries for ongoing trials. We also searched citation indexes, Web of Science, PubMed, and OpenGrey. We searched the reference lists of relevant studies and contacted experts in the field for any additional trials. There were no language restrictions. Randomised controlled trials (RCTs) comparing DHEA or T as an adjunct treatment to any other active intervention, placebo, or no treatment in women undergoing assisted reproduction. Two review authors independently selected studies, extracted relevant data, and assessed risk of bias. We pooled data from studies using fixed-effect models. We calculated odds ratios (ORs) for each dichotomous outcome. Analyses were stratified by type of treatment. We assessed the certainty of evidence for the main findings using GRADE methods. We included 29 RCTs. There were 1599 women in the intervention group and 1469 in the control group. Apart from three trials, the trial participants were women identified as 'poor responders' to standard in vitro fertilisation (IVF) protocols. The included trials compared either T or DHEA treatment with placebo or no treatment. Pre-treatment with DHEA versus placebo/no treatment: DHEA likely results in little to no difference in live birth/ongoing pregnancy rates (OR 1.30, 95% confidence interval (CI) 0.95 to 1.76; I² = 16%, 9 RCTs, N = 1433, moderate certainty evidence). This suggests that in women with a 12% chance of live birth/ongoing pregnancy with placebo or no treatment, the live birth/ongoing pregnancy rate in women using DHEA will be between 12% and 20%. DHEA likely does not decrease miscarriage rates (OR 0.85, 95% CI 0.53 to 1.37; I² = 0%, 10 RCTs, N =1601, moderate certainty evidence). DHEA likely results in little to no difference in clinical pregnancy rates (OR 1.18, 95% CI 0.93 to 1.49; I² = 0%, 13 RCTs, N = 1886, moderate certainty evidence). This suggests that in women with a 17% chance of clinical pregnancy with placebo or no treatment, the clinical pregnancy rate in women using DHEA will be between 16% and 24%. We are very uncertain about the effect of DHEA on multiple pregnancy (OR 3.05, 95% CI 0.47 to 19.66; 7 RCTs, N = 463, very low certainty evidence). Pre-treatment with T versus placebo/no treatment: T likely improves live birth rates (OR 2.53, 95% CI 1.61 to 3.99; I² = 0%, 8 RCTs, N = 716, moderate certainty evidence). This suggests that in women with a 10% chance of live birth with placebo or no treatment, the live birth rate in women using T will be between 15% and 30%. T likely does not decrease miscarriage rates (OR 1.63, 95% CI 0.76 to 3.51; I² = 0%, 9 RCTs, N = 755, moderate certainty evidence). T likely increases clinical pregnancy rates (OR 2.17, 95% CI 1.54 to 3.06; I² = 0%, 13 RCTs, N = 1152, moderate certainty evidence). This suggests that in women with a 12% chance of clinical pregnancy with placebo or no treatment, the clinical pregnancy rate in women using T will be between 17% and 29%. We are very uncertain about the effect of T on multiple pregnancy (OR 2.56, 95% CI 0.59 to 11.20; 5 RCTs, N = 449, very low certainty evidence). We are uncertain about the effect of T versus oestradiol or T versus oestradiol + oral contraceptive pills. The certainty of the evidence was moderate to very low, the main limitations being lack of blinding in the included trials, inadequate reporting of study methods, and low event and sample sizes in the trials. Data on adverse events were sparse; any reported events were minor. Pre-treatment with T likely improves, and pre-treatment with DHEA likely results in little to no difference, in live birth and clinical pregnancy rates in women undergoing IVF who have been identified as poor responders. DHEA and T probably do not decrease miscarriage rates in women under IVF treatment. The effects of DHEA and T on multiple pregnancy are uncertain. Data regarding adverse events were very limited; any reported events were minor. Research is needed to identify the optimal duration of treatment with T. Future studies should include data collection on adverse events and multiple pregnancy.

Transfer of embryos with positive PGT-M results: Genetic Counselors' perspectives and ethical considerations.

Increasing numbers of fertility patients use preimplantation genetic testing for monogenic conditions (PGT-M) during invitro fertilization (IVF). While PGT-M is primarily used to avoid implanting embryos with a monogenic condition, patients can request to transfer an embryo with the monogenic condition (positive embryo transfer), especially in cases where an IVF cycle results in no unaffected embryos. Transferring embryos with known disease-causing variants raises ethical concerns. There is limited understanding about how stakeholders in the assisted reproductive technology (ART) field approach these issues. In this study, genetic counselors were sent a survey to gather insight into their views about transferring embryos with different monogenic conditions. N = 99 genetic counselors completed the survey, 22 of whom had experience with patients requesting or deciding to transfer an embryo with a monogenic condition (positive embryo transfer experience). Most participants, including those with positive embryo transfer experience, were supportive of positive embryo transfer, regardless of the genetic condition. While participating genetic counselors were largely supportive of all patient decisions, they reported increased moral uneasiness around transferring embryos with life-limiting monogenic conditions, such as Huntington's disease. Further investigation into the experiences of genetic counselors who have experienced positive embryo transfer requests in practice can help delineate the ethical questions that ART providers face in this context and clarify how genetic counselors can contribute to establishing guidelines in the ART field.

Assessment of a Decade of Change in U.S. Assisted Reproductive Technology Cumulative Live-Birth Rates: 2004-2009 Compared With 2014-2020.

To assess the effects of demographic shifts, changes in contemporaneous clinical practices, and technologic innovation on assisted reproductive technology (ART) success rates by conducting an analysis of cumulative live-birth rates across different time periods, age groups, and infertility diagnoses. We conducted a retrospective cohort study of autologous linked cycles comparing cumulative live-birth rates over successive cycles from patients undergoing their first retrieval between 2014 and 2019 in the SART CORS (Society for Assisted Reproductive Technology Clinic Outcome Reporting System) database. All cycles reported for these individuals up to 2020 were included for analysis. We compared cumulative live-birth rates stratified by age and infertility cause with published data from the 2004-2009 SART CORS database. From 2014 to 2019, 447,042 patients underwent their first autologous index retrieval, resulting in 1,007,374 cycles and 252,215 live births over the period of 2014 to 2020. In contrast, between 2004 and 2008, 246,740 patients underwent 471,208 cycles, resulting in 140,859 births by 2009. Noteworthy shifts in demographics were observed, with an increase in people of color seeking reproductive technology (57.9% vs 51.7%, P <.001). There was also an increase in patients with diminished ovarian reserve and ovulatory disorders and a decrease in endometriosis, tubal, and male factor infertility ( P <.001). Previously associated with decreased odds of live birth, frozen embryo transfer and preimplantation genetic testing showed increased odds in 2014-2020. Preimplantation genetic testing rose from 3.4% to 36.0% and was associated with a lower cumulative live-birth rate for those younger than age 35 years ( P <.001) but a higher cumulative live-birth rate for those aged 35 years or older ( P <.001). Comparing 2014-2020 with 2004-2009 shows that the overall cumulative live-birth rate improved for patients aged 35 years or older and for all infertility diagnoses except ovulatory disorders ( P <.001). This analysis provides insights into the changing landscape of ART treatments in the United States over the past two decades. The observed shifts in demographics, clinical practices, and technology highlight the dynamic nature of an evolving field of reproductive medicine. These findings may offer insight for clinicians to consider in counseling patients and to inform future research endeavors in the field of ART.

Real clinical practice of infertility treatment in Russia: a collective opinion of 425 reproductologists

Introduction. Approaches to treatment of infertility have been progressively updated because the field of assisted reproductive technologies (ART) is a science-based symbiosis of the latest knowledge and advances in medicine, biology, and genetics. Today, a real-world clinical practice of a reproductive specialist needs to be assessed in the Russian Federation (RF) both in terms of a retrospectively analyzed development of RF in vitro fertilization (IVF) technologies and identifying promising approaches for infertility treatment in the future.Aim: analysis of current therapeutic tendencies and promising trends in real clinical practice of infertility in the Russian Federation.Materials and Methods. In 2022–2023 under the auspices of the Institute for Preventive and Social Medicine and the National Alliance for Public Health Advancement, a survey of reproductive doctors practicing at commercial and government ART centers was carried out. The questionnaire contained questions regarding describing a RF female patient’s portrait with an expected ovarian reserve and response to ovarian stimulation to propose a choice of ovarian stimulation protocol as well as basic and concomitant pharmacotherapy.Results. The opinion of 425 fertility doctors from 156 ART centers in 42 cities of the Russian Federation was assessed. A portrait of a female patient with infertility in the Russian Federation was determined in accordance with the ovarian reserve, expected response to gonadotropin-based stimulation (normal response – 40 %, hyporesponse – 40 %, hyperresponse – 20 % of patients). The basic pharmacotherapy in the stimulation protocol in the IVF program based on agonists and antagonists of gonadotropinreleasing hormone (GnRH), various gonadotropin-containing drugs in female patients with expected normal, hypo- and hyperresponse to ovarian stimulation was assessed. The dominant protocol consists of using GnRH antagonist most often observed in patients with hyper- (95 % of cases), normal (75 % of cases) and hypo-response (45.5 %). Preferences in the basic and concomitant pharmacotherapy in IVF programs were identified as well as current trends in embryo transfer in fresh and cryoprotocols (a tendency to freeze all obtained embryos - “freeze-all” strategy), preimplantation genetic testing methods (used in 30 % of protocols in normal responders, 60 % in hyporesponders and 10 % in hyperresponders) were described.Conclusion. Our study provides the most large-scale analysis of the real-world clinical practice of RF reproductive specialists. A portrait of a RF female patient with infertility, expected ovarian reserve and response to ovarian stimulation was described. Contemporary approaches to select stimulation protocol, basic and concomitant pharmacotherapy in real-world clinical practice were identified. The data obtained represent an important significant cross-section for current practical approaches in real-world practice of RF fertility doctors and can serve as the basis for assessing developing ART methods in the Russian Federation as well as be used to create an evidence base for analyzing future clinical and economic effectiveness of IVF programs in the Russian Federation.

Microfluidic chip as a promising evaluation method in assisted reproduction: A systematic review.

The aim of assisted reproductive technology (ART) is to select the high-quality sperm, oocytes, and embryos, and finally achieve a successful pregnancy. However, functional evaluation is hindered by intra- and inter-operator variability. Microfluidic chips emerge as the one of the most powerful tools to analyze biological samples for reduced size, precise control, and flexible extension. Herein, a systematic search was conducted in PubMed, Scopus, Web of Science, ScienceDirect, and IEEE Xplore databases until March 2023. We displayed and prospected all detection strategies based on microfluidics in the ART field. After full-text screening, 71 studies were identified as eligible for inclusion. The percentages of human and mouse studies equaled with 31.5%. The prominent country in terms of publication number was the USA (n = 13). Polydimethylsiloxane (n = 49) and soft lithography (n = 28) were the most commonly used material and fabrication method, respectively. All articles were classified into three types: sperm (n = 38), oocytes (n = 20), and embryos (n = 13). The assessment contents included motility, counting, mechanics, permeability, impedance, secretion, oxygen consumption, and metabolism. Collectively, the microfluidic chip technology facilitates more efficient, accurate, and objective evaluation in ART. It can even be combined with artificial intelligence to assist the daily activities of embryologists. More well-designed clinical studies and affordable integrated microfluidic chips are needed to validate the safety, efficacy, and reproducibility. Trial registration: The protocol was registered in the Open Science Frame REGISTRIES (identification: osf.io/6rv4a).

Laser-Guided Sperm Selection: Optimizing the Reproductive Success Rate in Assisted Reproductive Technology.

Assisted reproductive technologies (ART) enable these patient's spermatozoa to fertilize the oocyte and create viable and healthy offspring, but the effectiveness of the various procedures still has room to increase. In the field of assisted reproductive technology, the need to improve fertility results has led to the development of novel sperm selection strategies. Laser-assisted selectionof immotilesperm (LAISS) appears to be a promising strategy, harnessing the power of modern optical instruments to better the selection process and, ultimately, maximize the probability of successful fertilization. This technology takes advantage of sperm cells'distinctive features, such as shape, form, and motility patterns, that can be sensitively changed by laser forces. Using precision laser manipulation, spermatozoa with desirable features can be precisely targeted, improving the overall quality and viability of the sperm population. The existence of an elevated percentage of DNA-damaged sperm in a patient's ejaculation may be one of the key factors decreasing ART outcomes. As a result, one of the most difficult tasks in reproductive medicine is ensuring the best quality of spermatozoa utilized in ART, particularly with regard to genetic integrity. The most recent approaches for preparing and selecting human spermatozoa by LAISS techniquesare covered here, with an emphasis on those that have been shown to improve.

A Biomimetic Follicle‐Based Design for Engineering Reproductive Technologies

AbstractIn the field of assisted reproductive technologies, oocyte in vitro maturation (IVM) has emerged as a potential alternative to overcome the limitations associated with standard ovarian stimulation treatments. However, current IVM protocols lack standardization and yield oocytes of inferior quality compared to those matured in vivo. To address this issue, novel biomaterials like hydrogels offer distinct advantages in cell culture by providing a 3D cellular environment and facilitating easy adjustment and characterization of mechanical properties, such as hydrogel stiffness. Herein, a novel and reusable bilayer hydrogel system is presented that accurately mimics the mechanical properties of the microenvironment surrounding oocyte maturation. The system comprises an outer layer fabricated from either a 3D‐printed synthetic polymer (2‐vinyl‐4,6‐diamino‐1,3,5‐triazine, (VDT)) or a natural polymer (chitosan), along with an inner layer composed of alginate. By faithfully replicating the mechanical properties of native tissue within a 3D culture environment, this system significantly improves the quality and developmental capacity of oocytes, thus resulting in successful embryo development. Overall, this innovative system holds great potential for future medical research and applications in cell culture, thus representing a significant advancement in assisted reproductive technologies.

The Efficacy of Vitamin D Supplement in the Expression and Protein Levels of Endometrial Decidualization Factors in Women with Recurrent Implantation Failure.

Recurrent implantation failure (RIF) is a challenging situation for infertility specialists, and its treatment is introduced as a difficult case in the field of assisted reproductive technology (ART). Vitamin D (VD) is one of the supplements that have been suggested to improve the implantation process. In the present study, the effect of VD on the expression and protein levels of VD receptor (VDR), progesterone receptor (PR), prolactin (PRL), insulin-like growth factor binding protein-1 (IGFBP-1), and homeobox protein A10 (HOXA10) in the endometrial cells of unknown RIF women with and without VD deficiency were assessed by qRT-PCR and immunohistochemistry. Twelve women with unknown RIF and VD deficiency (≤ 20 ng/ml) and twelve women with unknown RIF without VD deficiency (≥ 30 ng/ml) from 2021 to 2022 were identified. Endometrial specimens were collected in the mid-luteal stage before treatment or pregnancy. In the group with VD deficiency, oral medication of VD 50,000 units was prescribed for 2 to 3 months and their serum levels of VD were re-measured, then an endometrial biopsy at the same stage of the menstrual cycle was performed. The expression and protein levels of VDR, PR, PRL, IGFBP1, and HOXA10 in RIF patients with VD deficiency were lower than the RIF patients without VD deficiency (P value < 0.05). Our findings suggest that VD can play a key role in the pregnancy process, especially during embryo implantation and decidualization of the endometrial cells.IRCT registration number: IRCT20220528055006N1, Registration date: 2022-10-15, Registration timing: retrospective.

HIF-1α is positively associated with endometrial receptivity by regulating PKM2.

Numerous advancements have been introduced into the field of assisted reproductive technology (ART) in the past four decades. Nonetheless, implantation failure is still a key limiting step for a successful pregnancy. Building of endometrial receptivity (ER) is essential for successful implantation. However, the fundamental biological processes and mechanisms of ER remain elusive. Our study investigates the function of hypoxia inducible factor-1α (HIF-1α) during ER establishment and shed lights on the novel molecular mechanism by which HIF-1α regulates ER-related gene expression network. Levels of HIF-1α, homeobox A10 (HOXA10), insulin-like growth factor-binding protein 1 (IGFBP1), pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA) in endometrial tissues were measured via real-time PCR, immunoblotting and immunohistochemistry. The correlation between HIF-1α and HOXA10, IGFBP1, PKM2, LDHA were analyzed separately. Ishikawa cells were treated with vector HIF-1α, HIF-1α-siRNA, and PKM2-siRNA. After transfection, the levels of HOXA10, IGFBP1, LDHA, and PKM2 were measured via real-time PCR and immunoblotting, and the lactate concentrations and cell migration of Ishikawa cells were measured. Levels of HIF-1α, IGFBP1, HOXA10, LDHA, and PKM2 were significantly decreased in recurrent implantation failure (RIF) patients and levels of HOXA10, IGFBP1, PKM2, and LDHA were correlated with HIF-1α in endometrium. Then in a cellular model established by HIF-1α vector and HIF-1α-siRNA, the expression of HOXA10, IGFBP1, LDHA, PKM2, and lactate concentrations were dramatically upregulated and downregulated. And the expression of HOXA10, and IGFBP1 were dramatically decreased by PKM2-siRNA. HIF-1α plays a crucial role in the building of ER through regulating glycolysis.

The modest impact of assisted reproductive technology on the second birth: insights from a population-based study in Lombardy, Northern Italy

BackgroundIn the field of assisted reproductive technology (ART), family rate is a neglected but emerging issue. The aim of the study was to investigate the epidemiological impact of ART on the second birth during the period 2007–2020 in Lombardy, Northern Italy. MethodsWe conducted a population-based study using administrative data from regional healthcare databases of Lombardy including first and second births occurred from 2007 to 2020. The proportion of deliveries after ART was calculated separately among first and second births. The probability of undergoing ART to achieve second birth compared to first one was estimated computing odds ratio (OR), crude and adjusted for maternal age, education, and nationality. We also assessed changes with age and calendar period. ResultsWe obtained a cohort including 553,190 first births and 317,976 second births. The proportion of ART babies among first and second births was 4.3% and 1.0% respectively (p < 0.001). The probability of undergoing ART to achieve second birth compared to first one, adjusted for age, education, and nationality, was 0.14 (95%CI: 0.13–0.15). The proportion of deliveries after ART increased with maternal age and along the calendar period but remained always markedly higher among first births rather than among second births. ConclusionART played a significantly lower role in the determinism of the conception of a second birth in comparison to the conception of a first one.

P-737 Progress in non-invasive embryo assessment with cell-free nucleic acids in blastocoel fluid

Abstract Study question Can cell-free nucleic acids (cfDNA) from blastocoel fluid (BF) after a trophectoderm (TE) biopsy be used as a non-invasive sample type to assess embryos? Summary answer Both BF and spent media carry comparable, highly fragmented cfDNA and cell-free RNA (cfRNA) which may reveal more about the quality of the embryo. What is known already Preimplantation genetic testing for aneuploidy (PGT-A) is commonly used by IVF clinics to screen embryos for any chromosomal abnormalities during the IVF process. Noninvasive preimplantation genetic testing (ni-PGT) is an emerging category of tools within the field of assisted reproductive technology. Currently, niPGT products have been developed for embryo aneuploidy detection using cfDNA released by the embryo into the spent media. Embryo spent media (ESM) carries cfDNA, which has the potential to be applied to evaluate the quality of the embryo. Previous studies have demonstrated that cfDNA in ESM is highly fragmented to the nucleosome level. Study design, size, duration The quality and quantity of cell free nucleic acid from forty BF-conditioned media (BFCM) samples were analyzed in this study. Embgenix™ Analysis Software was used to analyze and interpret sequencing data. For each sample, the concentration and fragmentation of cfDNA were examined and compared using generalized linear mixed models. To assess RNA quality at a picogram level, reverse-transcribed and amplified cDNA was used to represent the quality of cfRNA in BFCM. Participants/materials, setting, methods Embryos were washed and placed in individual biopsy media droplets for TE biopsy. After biopsy, blastocysts were collapsed, releasing BF into the droplet. The entire droplet was collected as BFCM. The Embgenix ESM Screen Kit was used to prepare sequencing libraries. The SMART-Seq® Single Cell Kit was used to evaluate the RNA quality. The BFCM cfDNA results were also compared to spent media profile that had already been obtained from a different cohort of embryos. Main results and the role of chance Amounts of cfDNA fragmentation detected in BFCM samples was comparable to ESM. Whole-genome amplification (WGA) yields correlated to the amount of cfDNA input but not the degree of cfDNA fragmentation. Informative sequencing reads and computed copy number variations (CNV) plot noise, as evaluated by distribution of log2 ratio spread (DLRS), also showed correlation and stable performance down to ∼2 pg of cfDNA input. We extracted detectable cfRNA from BFCM and created cDNA for RNA quality analysis. Our model demonstrates a significant correlation between cDNA length and RNA quality metrics, with a low DV200 of cfRNA from BFCM samples. The quantity and quality of cfDNA released into spent culture media by a developing embryo are comparable to the cfDNA released into BFCM upon TE biopsy, indicating that BFCM has potential as a noninvasive method for assessing the ploidy status of embryos. WGA yield, informative reads, and DLRS of BFCM samples were likewise comparable to data previously acquired using spent media samples. However, the severely fragmented cfRNA in these samples illustrate the inherent instability of RNA and the difficulty of utilizing RNA analysis to determine embryo health. Assays compatible with small RNA or microRNA (miRNA) are more appropriate for RNA-seq of BFCM. Limitations, reasons for caution Different clinics use varying methods for embryo culture and biopsy; the data reported here is from a single research center. The characteristic of samples may vary between clinics. Our assay estimates RNA quality using amplified cDNA; nonetheless, discrepancies between fragmented RNA and amplified cDNA may exist. Wider implications of the findings In PGT-A, BFCM samples are routinely discarded. Our findings imply BFCM samples contain considerable levels of cell-free nucleic acids which could also be used to screen embryo quality. BFCM samples, therefore, could be analyzed in conjunction with PGT-A to select and/or rank embryos for implantation. Trial registration number Not applicable

O-220 Artificial intelligence for embryo selection: ethical, social and regulatory issues

Abstract Study question What are the key ethical, social and regulatory issues raised by artificial intelligence technologies (AI) for embryo selection, and how might these be best managed? Summary answer Key issues with AI for embryo selection include deskilling, transparency, accountability, and fairness. These require attention to improve psychosocial and clinical outcomes in ART. What is known already Artificial intelligence (AI) technologies play a growing role in the assisted reproductive technology (ART) sector. Machine learning holds enormous promise for improving the selection of human embryos for transfer after IVF. Time-lapse imaging in conjunction with machine learning has the potential to standardise and automate embryo selection, improving clinical outcomes. Promising results have recently been published, and AI tools have reached the market. However, ethical and regulatory analysis has not kept pace with the technology. There has been negligible research on the ethical, social, and regulatory issues raised by the use of machine learning methods for embryo selection. Study design, size, duration A terrain-mapping review of the academic literature was performed to identify the key social, ethical and regulatory issues raised by AI for embryo selection. This is part of a multi-method study, collecting qualitative and quantitative data alongside ethical and regulatory analysis.The study is expected to take 1 year. Participants/materials, setting, methods A systematic review of the extant literature on the ethical, social, and regulatory issues raised by machine learning for embryo selection, combined with a narrative review of the broader literature on the use of AI in healthcare was undertaken. This review of ethical and regulatory issues will ultimately combine with data from semi-structured interviews and an online survey of ART patients and practitioners, including fertility specialists and embryologists, and ART regulators in Australia. Main results and the role of chance This paper reports on ethical and regulatory analysis of key issues that emerge from the use of AI for embryo selection. The use of AI in healthcare generally has raised serious concerns about deskilling and ‘dehumanization’(as roles traditionally performed by humans are displaced by technology), transparency, accountability, and fairness. This paper examines these issues in the ART context, to begin to develop guidance on how to best implement this technology in ways that balances the interests of all stakeholders and is consistent with maintaining public trust in the field of ART. Limitations, reasons for caution It is anticipated that much of the analysis of the social, ethical and regulatory issues will be generalisable internationally. However, the study prioritises one context - that of Australia. Some features of the Australian context may limit generalisability. Wider implications of the findings There is a need to address the ethical, social and regulatory issues that arise with the emergence of innovative technologies within ART to maintain public trust and ensure that psychosocial and clinical outcomes are improved. Further data collection on stakeholder views of machine learning for embryo selection will be required. Trial registration number Not applicable

P-292 It is feasible to carry out a large-scale multi-national Assisted Reproductive Technology Real World Data (RWD) collection prospectively, encompassing collected patient and treatment cycle information

Abstract Study question Is it feasible to carry out a large-scale multi-national Assisted Reproductive Technology Real World Data (RWD) collection prospectively, encompassing collected patient and treatment cycle information? Summary answer The creation of an international database collecting RWD is feasible. The quality and quantity of the data allow them to be used for research purposes. What is known already Real World Evidence (RWE) may help to answer clinical research questions that are relevant to a broad population of patients. For 40 years, Assisted Reproductive Technology (ART) treatment cycle data have been collected in national registries. The aggregated national data are further collated on an international level. These data are useful for describing secular trends in ART utilization and associated outcomes. However, registries often fall short in providing patient-level and treatment-cycle-level information for data collation and analysis. Furthermore, national registries may restrict access of raw data for open research, for political, infrastructural, or legal reasons. Study design, size, duration In a first phase, the OPERA database (Observational retrospective ProjEct for a Research database for ART procedures) included data from cycles recorded between January 2016 and December 2020 in eighteen clinics, providing a robust sample size for Real World Data analyses. Fondazione per la Ricerca Ospedale di Bergamo (FROM), together with expert clinicians in the ART field, promoted the OPERA project with the financial support from two pharmaceutical companies (Merck KGaA, IBSA SA). Participants/materials, setting, methods The Eighteen clinics located in Germany and Italy joining the OPERA data collection, have proven expertise in ART procedures and use MedITEX® DB. The study protocol was reviewed by the competent Ethic Committees and Data Protection Officers. Among the outcomes collected were the mean number of cycles, the pregnancy and birth rate per Embryo Transfer, and the pregnancy and birth rates as a function of female age. The first extraction was scheduled for December 2022. Main results and the role of chance Around 75,000 ART cycles were collected from the first ten participating centers. Among the around 45,000 cycles that have available fertilization information , 11,553 (25.7%) were the In-Vitro Fertilization treatments (IVF), 31,202 (69.3%) Intracytoplasmic Sperm Injection treatments (ICSI), and 2,282 (5.1%) a combination of the two techniques. Of the adopted stimulation protocols, 38.43% (10,538) of the total were with variable antagonists, 31.27% (8,574) were with a single antagonist, 24.31% (6,665) were with a long agonist, 5.51% (1,511) were with a short agonist, and 0.35% (96) were with fixed antagonists. The average number of oocytes retrieved is 11.28, with a median of 10.0. The average number of 2 Pronuclear Oocytes (2PN) obtained is 3.7, with a median of 3.0. Moreover, the average number of 8 cell embryos at day 3 is 2.0, with a median of 2.0. It was also recorded the rate of unsuccessful cycles with no oocytes retrieved (4.8%). Among the cycles collected, 2.9% of the total were from frozen oocytes. Most of the ET (40.0%) were performed 5 days after the oocyte retrieval. Limitations, reasons for caution Amassing ART cycle information does not compensate for the well-known insufficiencies of primary data quality, of information on confounders and of access to patient level data. Moreover, the technical risk of this project is the potential loss of participant confidentiality, mitigated through a full anonymization. Wider implications of the findings The OPERA project may facilitate the transition of ART surveillance from a national aggregate level to a large-scale individual patient and treatment cycle level. Furthermore, as an evolutionary path, the OPERA project may help building large and longitudinal databases, suitable for appropriate epidemiological research in ART. Trial registration number not applicable

Metabolomics and its applications in assisted reproductive technology.

Metabolomics, an emerging omics technology developed in the post-gene age, is an important part of systems biology. It interprets the pathophysiological state of the subject by quantitatively describing the dynamic changes of metabolites through analytical methods, mainly mass spectrometry (MS) and nuclear magnetic resonance (NMR). Assisted reproductive technology (ART) is a method used to manipulate sperm, oocytes, and embryos to achieve conception. Recently, several studies have reported that metabolomics methods can be used to measure metabolites in ART samples; these metabolites can be used to evaluate the quality of gametes and embryos. This article reviews the progress of research on metabolomics and the application of this technology in the field of ART, thus providing a reference for research and development directions in the future.

К вопросу о квалификации нарушений законодательства в сфере вспомогательных репродуктивных технологий

The presented work is devoted to the problems of legal evaluation of violations of law committed by medical workers in the field of assisted reproductive technologies. On the basis of the analysis of law enforcement practice and mass media the author made their classification, determined the basic characteristics necessary for the legal evaluation of such actions, and comes to the conclusion that it would be recommended to improve the Russian legislation.

Serum levels of anti-Müllerian hormone influence pregnancy outcomes associated with gonadotropin-releasing hormone antagonist treatment: a retrospective cohort study

As a specific predictor of ovarian reserve, serum anti-Müllerian hormone (AMH) has become an area of intense research interest in the field of assisted reproductive technology. We assessed the relationship between AMH levels and pregnancy outcomes in Chinese patients and investigate the influencing factors of cumulative live birth in patients with high AMH levels. A total of 1379 patients starting their IVF/ICSI cycle were divided into normal (Group A, 1.1–4.0 ng/ml, n = 639) and high (Group B, > 4.0 ng/ml, n = 740) groups by serum AMH levels. Live birth rate (LBR), cumulative live birth rate (CLBR) and cumulative clinical pregnancy rate (CCPR) were also investigated. Compared with Group A, Group B had a significantly higher CLBR (65.80% vs. 43.95%) and CCPR (76.77% vs. 57.14%), respectively. Binomial logistic regression analysis showed that age over 40 years, LH/FSH > 2.5, total Gn dose and Gn duration, and greater than 4000 ng/ml serum E2 levels on HCG day were significantly associated with CLBR in Group B. The AUC value of CLBR averaged 0.664 (ranging from 0.621 to 0.706) (p < 0.001). The patients with high AMH levels had higher CPR, higher LBR, and lower MR with no statistically significant differences, although there were significant improvements in CLBR. Advanced age (> 40 years) still impacted CLBR, even in women with good ovarian reserves. Consequently, it is still recommended that patients over 40 years old with high AMH levels actively receive IVF treatment if they seek to become pregnant. PCOS diagnoses did not influence the CLBR. In summary, this study showed that serum AMH levels could positively predict patient ovarian responses and further affect pregnancy outcomes.

Access to infertility care and ART treatment in India: A clinician's perspective

Infertility is a worldwide problem that is increasing with time. The cause of infertility can be due to either male or female factors or both. The food, environmental, occupational and psychological factors do contribute to infertility. The infertility and the present scenario of assisted reproductive technology (ART) in India with regard to the clinics, clinicians and regulatory mechanisms in vogue are discussed. The potential of India as a reproductive tourist destination and surrogacy issues is included. The social, economic, and family problems arising as a consequence of infertility are discussed. The status of ART in India is getting improved and the gap between the West and India is expected to be minimized with the influence of regulatory mechanisms introduced through ART Act in India. The salient features that have a bearing on the infertility treatment outcomes, which are being neglected, or recent findings of research are included with special reference to possible future developments in the field of ART.