Assisted Reproductive Technology Cycles Research Articles

The impact of extremely brief meditation and brief mindfulness interventions on assisted reproductive technologies success rates: A randomised controlled trial

ObjectiveTo investigate the effect of extremely brief meditation (EBMI) or brief mindfulness interventions (Brief MI) on pregnancy rate in women undergoing Assisted Reproductive Technology (ART). MethodsThis is a prospective, three-armed, randomized controlled trial with women undergoing ART cycle, age ranging from 18 to 50 years. In the day of embryo transfer, the patients randomized to Brief MI group received a 15-minute audio of mindfulness. They were instructed to practice it daily, starting from the day of embryo transfer to the day of the pregnancy test, leading to a total of 180–210 minutes. Women randomized to EBMI met once a week during the waiting time between the embryo transfer and pregnancy test day in the same virtual room with a meditator instructor for 40 minutes, totalizing two sessions (80 minutes). The pregnancy rate was assessed via a blood test to measure hCG performed 2 weeks after embryo transfer. ResultsA total of 68 women aged 37.5 ± 4.3y were included (EBMI, n = 24; Brief MI, n = 22 and CG, n = 22). Pearson's Chi-square test and Student's t-test for independent samples showed no significant differences between intervention and control groups. Both EBMI and Brief MI had no significant effect on pregnancy rate in women undergoing ART. ConclusionThis randomized control trial revealed that the extremely brief meditation (EBMI) or self-managed brief mindfulness intervention (Brief MI) had no significant effect on pregnancy rates in infertile women undergoing ART cycles. Trial registration number: NCT04058262.

Global legal trends in fertility interventions: A criminal justice perspective

The global decline in birth rates has heightened the urgency of addressing infertility, a condition that affects approximately one in six individuals worldwide. This paper explores the complex causes of infertility, including genetic predispositions, lifestyle choices, and environmental exposures, which collectively contribute to reproductive challenges in both men and women. The advent of Assisted Reproductive Technologies (ART), particularly In Vitro Fertilization (IVF), has revolutionized infertility treatment since 1978, providing hope to millions. Despite the remarkable advancements in ART, these technologies raise significant legal and ethical concerns, necessitating robust regulatory frameworks. This paper examines the historical development of ART, with a focus on global trends and data from ART registries, highlighting the steady increase in ART cycles worldwide. Furthermore, it delves into the legal and ethical challenges associated with ART, including issues related to donor rights, parental responsibilities, and the potential health risks for children born through these technologies. The paper advocates for continued refinement of ART practices and regulations to ensure safety, efficacy, and ethical integrity. It also underscores the importance of ongoing research into the long-term health implications for children conceived via ART and the broader societal impacts. By addressing these concerns, ART can continue to offer a viable solution to infertility while upholding human dignity and societal well-being.

Vaginal Progesterone Gel versus Intramuscular Progesterone for Luteal Phase Support in Suboptimal Responders Undergoing Assisted Reproductive Cycles

Background: The purpose of this research is to compare the efficacy of 8% micronized vaginal progesterone gel (VAG) at 180 mg daily versus intramuscular progesterone (IMP) in oil at 100 mg daily for luteal phase support (LPS) after fresh single embryo transfer (SET) in Patient-Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) Group 1b patients, and to ascertain whether the type of LPS predicts live birth in these patients. Methods: A total of 2420 assisted reproductive technology (ART) cycles performed in Ondokuz Mayıs University IVF Unit were analysed retrospectively. The data of POSEIDON Group 1b (unexpected suboptimal responders) who underwent antagonist in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles were included. All patients were categorized into groups according to the form of LPS, specifically VAG and IMP. Pregnancy, clinical pregnancy rate (CPR), live birth rate (LBR), spontaneous abortion rate and predictors of live birth (age, infertility duration, body mass index (BMI), type of progesterone used for luteal support, serum day 3 estradiol, serum progesterone on the day of human coryonic gonadotrophin (HCG), total duration of induction, serum estradiol on the day of HCG, the total number of oocytes retrieved, number of mature oocytes obtained, average gonadotropin dose per day, total gonadotropin dose administered and total number of embryos retrieved) were analyzed. Results: There was no statistically significant difference between the micronized VAG and IMP groups in terms of age (31 (23–35) vs. 27 (23–35), p = 0.319). There were no statistically significant differences in pregnancy outcomes between the two groups concerning CPR per transfer (70.6% vs. 75.6%; p = 0.364), ongoing pregnancy per cycle (36.2% vs. 39.5%; p = 0.577), and LBR per cycle (34.4% vs. 36.1%; p = 0.785). The spontaneous abortion rates (36.2% vs. 36.8%; p = 0.921) were similar between VAG and IMP groups. The type of LPS did not emerge as a parameter predicting pregnancy (odds ratio (OR): 0.718, 95% confidence interval (95% CI): 0.652–1.313, p = 0.451), clinical pregnancy (OR: 0.598, 95% CI: 0.592–1.289, p = 0.562) and live birth (OR: 0.802, 95% CI: 0.661–1.202, p = 0.580). The logistic regression analysis aimed at assessing the influence of confounding factors, namely age, BMI, and duration of infertility on pregnancy rate, CPR and LBR, did not reveal statistically significant results (p > 0.05). Conclusions: VAG 180 mg daily provide similar pregnancy outcomes compared to 100 mg daily IMP in POSEIDON Group 1b patients undergoing antagonist fresh IVF/ICSI cycles.

Assessment of embryologist sufficiency and associated regional disparities in Japanese assisted reproduction facilities using nationwide survey data (IZANAMI project).

This study aims to comprehensively examine the employment and practices of embryologists in Japan's assisted reproductive technology (ART) laboratories, focusing on the impact of various factors such as ART cycle numbers, add-ons, and regional differences. Additionally, it seeks to assess the extent to which Japanese ART facilities meet international minimum standards set by the American Society for Reproductive Medicine (ASRM). A survey was conducted from December 2021 to February 2022 among 621 ART facilities in Japan. The study categorized facilities into five ART cycle groups and compared the number of embryologists across these groups. It also examined the correlation between the number of embryologists, ART cycles, add-ons, and regional differences. Data were analyzed using linear regression and multiple linear regression analyses. The study's findings revealed a significant correlation between the total number of embryologists at each facility and the ART cycles. Notably, there were significant differences in the number of embryologists across all ART cycle categories. Of the 435 facilities, only 44.6% met the ASRM minimum embryologist staffing requirement. The regression analysis further highlighted the significance of ART cycles and preimplantation genetic testing for aneuploidies as factors. Moreover, the number of embryologists stationed at urban facilities was significantly higher than at nonurban facilities, indicating a potential regional disparity. In Japan, it was first found that more than 50% of ART facilities do not have sufficient embryologists in place relative to the number of ART cycles. Furthermore, the add-ons and regional differences affect the placement of embryologists.

Preliminary Report of the Effects of Platelet-Rich Plasma on the Ovarian Function and Oocyte Quality in Women with Ovarian Failure

This study investigated the effects of platelet-rich plasma (PRP) treatment on ovarian function and pregnancy outcomes in three patients with severe reduction of ovarian reserve. The patients had previously undergone multiple cycles of assisted reproductive technology (ART) without favorable results. Prior to PRP treatment, follicle-stimulating hormone (FSH), estradiol (E2), and anti-Mullerian hormone (AMH) levels were assessed. PRP was administered through intraovarian injection. Hormonal assessments were performed at 6–7 months after the first PRP injection. The results showed major improvements in ovarian function, as evidenced by decreased FSH levels and increased AMH levels in all three patients. The number of mature oocytes retrieved per cycle and the ovum-to-blastocyst rate were also improved. All the patients achieved successful pregnancies and gave birth to healthy infants. These findings suggest that PRP may enhance ovarian function, oocyte quality, and pregnancy outcomes in patients with severely reduced ovarian reserve. Further research is necessary to validate these results and explore the underlying mechanisms.

The Impact of Endometriosis on Reproductive Outcomes in ART Cycles.

Endometriosis is defined as the existence of endometrial glands and stroma outside the uterine cavity. This disease is responsible for about 15% of the indications for assisted reproductive technologies (ART). This study is a retrospective cross-sectional study on 1382 women aged 18-42 who underwent ART in Yazd Reproductive Sciences Institute during 2018-2022. Women were divided into two groups: women with endometriosis (N = 173) and women with a tubal factor or unexplained infertility as the control group (N = 1209). Chemical and clinical pregnancy rates and live birth rates were compared. Women with endometriosis had significantly (P < 0.001) lower retrieved oocytes (7.73 ± 5.52 vs 11.53 ± 7.46), metaphase II oocytes (6.27 ± 4.72 vs 9.37 ± 6.62), and the total number of obtained embryos (3.95 ± 3.52 vs 6.13 ± 5.02). Chemical (P = 0.001) and clinical (P = 0.028) pregnancy rates were lower in women with endometriosis, while live birth rates showed no difference between the two groups (P = 0.069). The findings of this study showed that endometriosis can disturb reproductive outcomes after ART.

Evaluation of ovarian reserve and the assisted reproductive technology (ART) cycles’ outcome as well as the relapse rate within one year after ART in women with multiple sclerosis: a case-control study

ObjectiveTo compare the ovarian reserve and the results of infertility treatment, as well as to investigate the relapse rate in the first year after the assisted reproductive technology (ART) cycle in patients with multiple sclerosis (MS) referred to Royan Institute.Materials and methodsThis retrospective study was carried out to evaluate all women diagnosed with MS and referred to Royan Institute for assessment and treatment of possible infertility between 2011 and 2022. The control group consisted of randomly selected healthy women with tubal factor infertility who were referred for treatment during the same time period and matched in terms of age. A comparison was made between groups in terms of ovarian reserve and infertility treatment outcomes. Additionally, patients with MS who met the criteria were monitored via telephone to evaluate the symptoms, disability and relapse rate both pre- and post-ART.ResultsOver the course of a decade, the database documented a total of 60 cases diagnosed with MS. Upon examination of the records, it was found that in 27 patients only admission was done without any hormonal assessment or infertility treatment cycle and 5 patients proceeded with the intrauterine insemination cycle. Eventually, 28 women with MS underwent the ART cycle and all of them were treated with interferon beta, glatiramer acetate, or some oral disease modifying therapies. No statistically significant difference in terms of the basal levels of luteinizing hormone, follicle-stimulating hormone and anti-Müllerian hormone was found between the MS and control groups (P > 0.05). Two groups were comparable in terms of menstrual status. The study revealed that both groups exhibited similarities in terms of the controlled ovarian stimulation protocol and duration, the dosage of gonadotropin administered, as well as the ovarian response type, clinical pregnancy rate, and live birth rate (P > 0.05). After follow up, only 2 patients (9.5%) reported relapse of symptoms within one year after ART.ConclusionThe ovarian reserve and ovarian stimulation cycle and pregnancy outcomes following the ART cycle in MS patients were similar to the age-matched control group. The relapse rate of multiple sclerosis did not show a significant increase within a year following the ART cycle.

Risk Factors of Pregnancy Failure in Infertile Patients Undergoing Assisted Reproductive Technology

Background: Assisted Reproductive Technology (ART) represents a critical advancement in the treatment of infertility, providing hope to many couples struggling to conceive naturally. Despite its success, pregnancy failure remains a significant concern, influenced by various factors such as age, BMI, and underlying medical conditions. Objective: The main objective of this study was to identify the risk factors associated with pregnancy failure in infertile patients undergoing ART treatments. Methods: This clinical audit was conducted at Bahria International Hospital, Rawalpindi, from January 2023 to January 2024. Data were collected from 85 patients undergoing ART treatments, including In Vitro Fertilization (IVF) and Intracytoplasmic Sperm Injection (ICSI). The study included comprehensive demographic information, clinical history, ART cycle details, laboratory results, and lifestyle factors. Pregnancy failure was defined as either biochemical pregnancy loss or clinical pregnancy loss. Ethical approval was obtained, and data were analyzed using SPSS version 25. Descriptive statistics summarized patient characteristics, while comparative analysis and multivariate logistic regression were used to identify significant risk factors. Results: The study included 85 patients with a mean age of 34.5 years. Those experiencing pregnancy failure had a higher mean age of 36.2 years compared to 33.2 years in those without pregnancy failure. The mean BMI was higher in the pregnancy failure group (26.0 kg/m²) versus the no pregnancy failure group (23.8 kg/m²). Significant risk factors for pregnancy failure included older age (OR=1.15, 95% CI 1.05-1.25, p=0.002), higher BMI (&gt;25 kg/m²) (OR=2.45, 95% CI 1.10-5.47, p=0.03), and the presence of underlying medical conditions (OR=1.90, 95% CI 1.02-3.55, p=0.04). Conclusion: Older age, higher BMI, and underlying medical conditions significantly increased the risk of pregnancy failure in infertile patients undergoing ART. Personalized treatment approaches addressing these risk factors could improve ART outcomes and enhance the chances of successful pregnancies.

The efficacy of evening primrose seed oil supplements on ART outcomes: A triple-blinded randomized placebo-controlled clinical trial

BackgroundEvening primrose oil (EPO) has been extensively documented for its potential benefits in various medical conditions, including gestational diabetes, inflammatory diseases, cyclic breast pain, cancer, premenstrual syndrome, menopausal syndrome, and female reproductive disorders. ObjectivesThe aim of this study was to investigate the impact of evening primrose oil (EPO) supplementation on the outcomes of assisted reproductive technology (ART). MethodsA randomized, triple-blinded, placebo-controlled clinical trial was conducted. A total of 84 infertile women who were candidates for intracytoplasmic sperm injection (ICSI) were randomly assigned to either the EPO supplementation group or the placebo (p) group with a 1:1 ratio. The EPO capsule was given from day 1–2 of the ART cycle at a dosage of 1000 mg every eight hours for two weeks. Finally, the ART outcomes parameters as well as the treatment side effects were evaluated. ResultsThe results illustrated no statistically significant disparities between the groups in terms of the number of oocytes retrieved, ovarian sensitivity index (OSI), rate of fertilization, and number and quality of embryos (p>0.05). However, a notably enhanced incidence of pregnancy and implantation rates in the EPO group was observed when compared to the P group (42.9 % vs. 17.4 % and 23±30.5 % vs. 10.87±26 %, respectively). Moreover, none of the patients experienced side effects from the intervention. ConclusionsEPO consumption for two weeks could improve ART outcomes by increasing implantation and pregnancy rates without significantly affecting the number of mature oocytes, rate of fertilization, and the quantity and quality of embryos. These findings highlight the significance of a maternal preconception diet.

Comparison of the effect of dydrogesterone and natural micronized progesterone for luteal-phase support in assisted reproductive technology cycles: A single-blind randomized clinical trial study.

One of the causes of preterm labor and recurrent abortion is progesterone deficiency in the luteal phase. The aim of the study was a comparison of the effect of oral dydrogesterone and vaginal progesterone for luteal-phase support (LPS) in assisted reproductive technology cycles (ART). This randomized clinical control trial study was conducted on 207 infertile women. Samples were randomly divided into two groups. The first group received a natural micronized vaginal progesterone (MVP) of 400 mg once daily and the second group received dydrogesterone (Duphestone) 20 mg twice daily. Then chemical pregnancy, abortion, and live births were compared in two groups. The results of the study showed that the vaginal form of the drug could increase the chance of pregnancy (positive β-human chorionic gonadotropin) versus the oral form. According to the results of multiple logistic regression analysis after adjusting for other variables, the live birth rate in the vaginal group was more than five times that of the oral group (odds ratio = 5.07; 95% confidence interval = 1.24-20.65; p = 0.023). The vaginal form of the progesterone could increase the chance of pregnancy and the outcome of fertility (live birth). Thus, vaginal progesterone is effective for LPS in women undergoing fresh embryo transfer.

Intracytoplasmic sperm injection versus conventional in vitro insemination in couples with non-male infertility factor in the ‘real-world’ setting: analysis of the HFEA registry

BackgroundIn assisted reproductive technology (ART), the choice between intracytoplasmic sperm injection (ICSI) and conventional in vitro insemination (IVF) remains a pivotal decision for couples with female or unexplained infertility. The hypothesis that ICSI may not confer significant improvements in live birth rates in the absence of a male infertility factor was explored in this study.MethodsThis was a retrospective collection of data recorded by the Human Fertilisation and Embryology Authority (HFEA) in the UK from 2005 to 2018 and analysed through regression analysis models on both the entire dataset and a matched-pair subset. First fresh ART cycles were analysed according to the insemination technique in order to compare live birth as the main outcome. Cycles were included if complete information regarding infertility cause, female age, number of oocytes retrieved, allocation to ICSI or IVF, and treatment outcome in terms of live birth was available. Matching was performed at a 1:1 ratio between IVF and ICSI cycles according to the cause of infertility, female age, number of oocytes, and year of treatment.ResultsThis study, based on 275,825 first cycles, revealed that, compared with IVF, ICSI was associated with higher fertilization rates and lower cycle cancellations rates. However, ICSI was associated with a lower chance of implantation and live birth than IVF in cycles with female-only infertility: in the entire dataset, the adjusted odds of having a live birth decreased by a factor of 0.95 (95% CI 0.91–0.99, p = 0.011), while in the matched-pair analyses it decreased by a factor of 0.91 (95% CI 0.86–0.96, p = 0.003) using ICSI compared to IVF. For unexplained infertility cycles, the adjusted odds ratios for live birth in ICSI compared to IVF cycles were 0.98 (95% CI 0.95–1.01) in the entire dataset and 0.97 (95% CI 0.93–1.01) in the matched-pair analysis.ConclusionsCompared with IVF, ICSI was associated with a reduction in live births when ART was indicated due to female-only factors. Additionally, no significant improvements were associated with the use of ICSI in cycles with unexplained infertility. Our findings impose a critical reevaluation regarding the use of ICSI over IVF for cases with female-only factors and unexplained infertility.

P-212 Balancing success and safety in assisted reproductive technologies cycles: the outcomes of transferring poor-quality blastocyst or day 5 slow-growing embryos with good-quality blastocyst

Abstract Study question Does transferring two mixed-quality embryos improve the live birth rate (LBR) without increasing the multiple gestation rate compared to the single good-quality blastocyst (GQB) transfers? Summary answer The transfers of single GQB and two mixed-quality embryos show similar LBRs, however, the multiple gestation rate was significantly higher in double embryo transfer groups. What is known already Due to higher LBR after blastocyst transfer, the single embryo transfer (SET) strategy has gained popularity worldwide. Despite that double-embryos transfers (DET) demonstrate higher LBR than SET, multiple gestation rates (MGRs) are higher in DET. To reduce MGR but still accomplish high LBR, DETs could be performed using embryos of mixed-quality. It has been suggested that the transfer of GQB with poor-quality blastocyst (PQB) could increase LBR without increasing MGR. Alternatively, when the embryo transfer is scheduled in a fresh cycle, the DET could be performed with GQB and day 5 slow-growing embryo (SGE) – early blastocyst or morula. Study design, size, duration This study included assisted reproductive technologies (ART) cycles with fresh embryo transfer on day 5, between 2015 and 2021, for patients under 34 years. Selected ART cycles were assigned into five groups: SET with GQB (SET-GQB, n = 754); DET with two GQBs (DET-GQB, n = 306); DET with one GQB and one PQB (DET-GP, n = 75); DET with one GQB and one day 5 SGE (DET-GS, n = 386), DET with two day 5 SGE (DET-SGE, n = 209). Participants/materials, setting, methods According to Gardner and Schoolcraft’s grading system, blastocyst morphological assessment was performed on day 5. Blastocysts graded as AA, AB, BA, and BB with a degree of expansion ≥3 were classified as GQBs, whereas blastocysts graded ВС, СВ, СС with a degree of expansion ≥3 were classified as PQBs. Day 5 morulas and blastocysts with degree of expansion 1 were classified as slow-growing embryos. The cycles with donor gametes, preimplantation genetic testing were excluded. Main results and the role of chance The LBR was significantly higher in DET-GQB than in SET-GQB [53,59% (164/306) vs 40,58% (306/754); P &amp;lt; 0,001]. There were no significant differences in implantation rate (IR) and miscarriage rate (MR) between SET-GQB and DET-GQB [47,88% (361/754) vs. 44,12% (270/612) P = 0,165], [12,19% (44/361) vs. 10,00% (27/270) P = 0,389]. However, the MGR was significantly higher in DET-GQB compared to SET-GQB [36,59% (60/164) vs 1,31% (4/306) P &amp;lt; 0,001]. When SET-GQB was compared with DET-GS, DET-GP there were no significant differences in LBR: [40,58% (306/754) vs. 39,64% (153/386) P = 0,757; vs. 41,33% (31/75) P = 0,899]. The IR was significantly higher in SET-GQB than in DET-GS and DET-GP [47,88% (361/754) vs. 30,70% (237/772) P &amp;lt; 0,001; vs. 30,00% (45/150) P &amp;lt; 0,001]. There were no significant differences in MR between SET-GQB and DET-GS, DET-GP [12,19% (44/361) vs. 17,30% (41/237) P = 0,079; vs. 11,11% (5/45) P = 0,834]. However, the MGR was significantly lower in SET-GQB compared to DET-GS, DET-GP [1,31% (4/306) vs. 18,95% (29/153) P &amp;lt; 0,001; vs. 22,58% (7/31) P &amp;lt; 0,001]. The IR and LBR were significantly higher in SET-GQB compared to DET-SGE [47,88% (361/754) vs 16,99% (71/418) P &amp;lt; 0,001], [40,58% (306/754)vs 19,14% (40/209) P &amp;lt; 0,001]. The MR and MGR were significantly lower in SET-GQB than in DET-SGE [12,19% (44/361) vs 32,39% (23/71) P &amp;lt; 0,001], [1,31% (4/306) vs 15,00% (6/40) P &amp;lt; 0,001]. Limitations, reasons for caution The study is limited due to the uneven distribution and a low number of participants in group DET-GP. Blastocyst morphological assessment remains subjected to a human factor. It was impossible to form a group where two PQBs were transferred, as there were only a few cases of such transfers. Wider implications of the findings Transferring an additional poor-quality embryo (poor-quality blastocyst or day 5 slow-growing embryo) does not increase the live birth rates. However, it significantly raises the multiple gestation rate. Despite the low live birth rate when two day 5 slow-growing embryos are transferred, the multiple gestation rate significantly increases, compared to SET. Trial registration number Not applicable

P-206 Unveiling the elasticity of zona pellucida: shifting focus to a neglected embryonic feature

Abstract Study question Is it feasible to quantitatively assess the elasticity of the zona pellucida, and how does this measurement correlate with blastocyst features? Summary answer The elasticity of the zona pellucida can be quantitatively evaluated, demonstrating a correlation with distinct developmental stages and morphological features of blastocysts. What is known already Embryologists have primarily focused on assessing morphokinetic and morphological features of embryos to enhance success rates in assisted reproduction technology cycles. However, the zona pellucida (ZP) has often been overlooked as a potential marker of embryonic quality. Previous studies have established a correlation between the thickness of the ZP and implantation rates in cleavage-stage embryos. Yet, the comprehensive attributes of the ZP in blastocysts remain under-explored, with critical aspects such as its elasticity receiving scant attention. Study design, size, duration A retrospective analysis was conducted on 254 blastocysts from 103 patients. For each blastocyst, two images were captured: one prior to and another following lased-induced artificial shrinkage. This study focused on assessing ZP elasticity by comparing its thickness during blastocele pressure-induced distension and subsequent to blastocyst collapse. Variations in thickness were interpreted as reflections of pressure release. To ensure the reliability and accuracy of data, measurements were performed by two independent operators. Participants/materials, setting, methods Measurements were performed using ImageJ software. Operators executed twelve radial assessments of ZP thickness at 30-degree intervals and three additional measurements of the area within the ZP. These measurements were averaged for analysis. The ZP re-expansion percentage post-laser collapse was determined by comparing the change in thickness relative to the initial thickness. Linear regression and Spearman’s correlation were employed to examine the relationships among ZP re-expansion, thickness, enclosed area, patient age, and blastocyst features. Main results and the role of chance The average ZP thickness prior to freezing (Pre-ZPT) was 5.1 ± 2.0 micrometers, increasing to 8.6 ± 2.0 micrometers following collapse. The mean blastocyst diameter at the time of freezing was 192 ± 17 micrometers, with ZP re-expansion averaging 82.1%. A strong correlation was observed between Pre-ZPT and post-collapse thickness, with a coefficient of 0.75 (P = 4.8 × 10−47). Pre-ZPT showed a significant inverse and non-linear relationship with pre-collapse blastocyst diameter (Pre-BD), as assessed by Spearman’s correlation (P value: 2.9 × 10−³¹). Additionally, a linear correlation was observed between Pre-BD and the percentage of ZP re-expansion post-collapse (P value: 3.8 × 10−²¹). Given the strong interdependence of these parameters, reflecting expected behavior from a semi-elastic sheath undergoing stretching, linear correlation between Pre-BD and re-expansion percentage was used to define ZP elasticity. Deviations from average behavior were normalized into percentiles and analyzed against patient age and blastocyst characteristics. Multivariate regression, adjusted for variables including Pre-ZPT, revealed a strong inverse association between blastocyst elasticity and freezing day, with a decrease of 16.8 percentiles on average (P value: 4.9 × 10−6). Conversely, a positive association was identified with poor-quality blastocysts, which showed an average increase of 12.4 percentiles in elasticity (P value: 1.5 × 10−³). No significant correlation emerged between ZP elasticity and patient age Limitations, reasons for caution This preliminary study was limited to the evaluation of the morphological and developmental characteristics of blastocysts, without delving into clinical outcomes. It is critical to note that blastocyst quality assessment is influenced by operator interpretation, which introduces a degree of variability into the morphological evaluation process. Wider implications of the findings Evaluating the elasticity of the ZP, a relatively unexplored aspect, might provide insights into its predictive value of blastocyst competence and subsequent successful clinical outcomes following embryo transfer. Such an analysis could significantly enrich our understanding of embryonic reproductive competence. Trial registration number not applicable

P-330 The impact of adenomyosis on pregnancy outcomes, from conception to birth- a systematic review and meta-analysis

Abstract Study question What is the impact of adenomyosis and its phenotypes on spectrum of outcomes ranging from conception to birth? Summary answer Adenomyosis has a negative impact on implantation with reduced clinical pregnancy and live birth rate and increased risk of miscarriage and perinatal morbidity. What is known already Current evidence, including meta-analyses, on the impact of adenomyosis on reproductive outcomes is conflicting. There are data suggesting that adenomyosis has a negative impact on pregnancy outcomes whereas some studies have suggested that adenomyosis appears inert, with no impact on reproductive functions. A wide variation has been observed in the baseline population, type of Assisted Reproductive Technology (ART) stimulation protocol, number, order and type of ART cycles across the pooled observational studies. Alongside, there may be a spectrum of adenomyosis characteristics like the disease type, location, severity, and presence of coexisting endometriosis, resulting in heterogeneity and our interpretation of evidence. Study design, size, duration For this systematic review and meta-analysis, a comprehensive search was conducted in MEDLINE, EMBASE, CINAHL Plus, Web of Science Core Collection, Clinicaltrials.gov and WHO ICTRP from inception until January 2024 with no language restriction. Observational studies were included with participants as women with natural and/or medically assisted reproduction (MAR) conception, exposure as adenomyosis diagnosed on imaging, histology or using WHO International Classification of Disease 10th edition (ICD-10) code (N80.0) and comparator as women without adenomyosis. Participants/materials, setting, methods Data was included from 51 observational studies for the meta-analysis of pregnancy and obstetric outcomes. ROBINS-E tool (Risk Of Bias In Non-randomized Studies-of Exposure) was be used to assess the risk of bias. Odds ratio (OR) from individual studies were pooled using random-effects model to summarise the estimate for dichotomous outcomes with 95% confidence interval (CI) and mean differences for continuous outcomes. This was supplemented by sensitivity analyses. Clinical heterogeneity was assessed with I² statistics. Main results and the role of chance Women with adenomyosis had reduced odds of implantation (OR = 0.78; CI: 0.72-0.86), lower clinical pregnancy (OR = 0.87; CI: 0.82-0.92), higher miscarriage (OR = 1.51; CI: 1.44-1.58), and lower live birth (OR = 0.56; CI: 0.50-0.63) compared to those without. Both, diffuse and focal adenomyosis were associated with lower live birth (OR = 0.56; CI: 0.45-0.72; diffuse and OR = 0.56; CI: 0.45-0.70; focal). The miscarriage risk was higher in junctional zone adenomyosis (OR = 4.04; CI: 1.17-13.94) compared to outer myometrium adenomyosis. The negative impact of adenomyosis was evident in subgroups of women undergoing donor oocyte cycles (OR = 0.62; CI: 0.50-0.76; live birth and OR = 1.83; CI: 1.26-2.66; miscarriage) and first ART cycle (OR = 0.55; CI: 0.48-0.65; live birth and OR = 2.16 CI: 1.72-2.71; miscarriage). Conversely, those with euploid embryo transfer, had a higher odds of miscarriage (OR = 1.90; CI:1.05-3.43) with no significant impact on live birth (OR = 0.78; CI: 0.52-1.19). The impact continued perinatally, including pre-eclampsia (OR = 1.32; CI: 1.23-1.41), small for gestational age (OR = 1.323; CI:1.25-1.40), placenta previa (OR = 3.99, CI: 3.53-4.51), caesarean section (OR = 1.97; CI:1.89-2.05), and low Apgar scores (OR = 0.911; CI:0.88-0.96). Limitations, reasons for caution The inherent heterogeneity among the included observational studies was high; however, subgroup analyses for type of ART cycle, number, and order of ART cycle and by phenotype of adenomyosis had low heterogeneity. This warrants caution when interpreting pooled outcome estimates for pregnancy and obstetric outcomes across general population of women. Wider implications of the findings Adenomyosis has a direct and negative impact on fertility and pregnancy outcomes by virtue of impaired implantation and trophoblastic function. Hence, adenomyosis needs to be factored in when counselling women about the success of MAR cycles and requires closer monitoring in pregnancy as a high-risk pregnancy. Trial registration number not applicable

P-014 Extracellular vesicles (EVs) from female reproductive tracts positively affect sperm capacitation and progressive motility

Abstract Study question Do EVs from human follicular fluid (FF-EVs), cervicovaginal fluid (CVF-EVs), and endometrial stromal cells spent medium (ESCs-EVs) induce sperm capacitation and enhance sperm motility? Summary answer In humans, EVs from different female reproductive tracts actively contribute to sperm maturation by inducing capacitation and enhancing sperm progressive motility. What is known already In the human body, EVs represent crucial players in cell-to-cell communication. EVs presence has been detected also in the female and male reproductive systems, specifically in seminal, follicular, oviductal, endometrial and vaginal fluid, as well as in embryo secretions. Moreover, EVs have been shown to be of pivotal importance in the fertilization process, as they support the maturation of spermatozoa and oocytes, as well as embryos in their development and endometrial implantation. The majority of these studies, though, have been conducted in animal models, underscoring the necessity to replicate analogous investigations also in humans. Study design, size, duration Follicular fluid (FF, n = 8), cervicovaginal fluid (CVF, n = 20) and endometrial tissue (n = 8) samples were collected from women undergoing assisted reproductive technology (ART) cycles at San Raffaele Hospital Fertility Centre (Milan). CVF were collected 2 and 7 days after the LH peak (CVF LH + 2 and CVF LH + 7, respectively). ESCs-EVs were isolated from both decidualized (dESCs-EVs) and not decidualized (eESCs-EVs) endometrial cells. Semen samples (n = 15) were collected from normozoospermic men. Participants/materials, setting, methods EVs were isolated using differential centrifugations and characterized using Transmission Electron Microscopy (TEM), Nanoparticle Tracking Analysis (NTA), and western blotting (WB). EVs capture by spermatozoa was assessed using flow cytometry. EVs impact on sperm progressive motility was evaluated following WHO guidelines. EVs potential to induce sperm capacitation was examined through sperm acrosome reaction (AR) induction using a Ca2+ ionophore, followed by Coomassie blue staining. All experiments were performed using EVs at 50 and 100 μg/mL. Main results and the role of chance Isolated EVs displayed comparable size, with mean diameters ranging from 147,9±11,6 nm to 168,1±6,2 nm (mean ± SEM) and average concentrations from 9,53E+10 ± 8,11E+09 to 2,70E+11 ± 3,49E+10 particles/ml (mean ± SEM). TEM analysis confirmed their round-shaped morphology and structural integrity, while WB confirmed their positivity for EVs markers (Alix, TSG101, CD63, CD9). Spermatozoa efficiency in capturing these fluorescently-labeled EVs, measured as the percentage of fluorescence-positive spermatozoa, reached up to 3,6±1,1% for FF-EVs, 12,1±3,7% for CVF-EVs and 9,4±1,9% for ESCs-EVs (mean ± SEM). Sperm cells co-incubated with any EVs group maintained unaffected vitality. Following a 4-hour incubation with EVs, a rise in the proportion of progressively motile spermatozoa was observed, with percentages of progressively motile spermatozoa ranging from a minimum of 45,4±3,8% for CVF-EVs LH + 7 to a maximum of 52,7±2,7% for dESCs-EVs (mean ± SEM). This increase resulted to be statistically significant (p &amp;lt; 0.05 and p &amp;lt; 0.01, respectively) compared to the untreated (UT) condition, which exhibited 26,2±0,7% of progressively motile sperm cells. Spermatozoa that completed the AR, indicating capacitation, after 4-hour incubation with EVs resulted to be up to 25,8±3,2% for FF-EVs, 35,0±6,6% for CVF-EVs and 26,9±3,0% for ESCs-EVs, compared to an average of 13% in the UT control. Limitations, reasons for caution This study constitutes a pilot investigation characterized by a limited sample size, necessitating larger cohorts to validate results. Wider implications of the findings Studied EVs may exert beneficial effects on capacitation and progressive motility also on asthenozoospermic (AS) men’s spermatozoa. Therefore, they could be used in ART cycles to prime spermatozoa from AS men and increase the percentage of sperm cells displaying progressive motility, potentially favouring fertilization via classical IVF instead of ICSI. Trial registration number not applicable

P-750 Is maximalization of the ovum pick-up (OPU) procedure beneficial for the outcome of assisted reproductive technology (ART) cycles?

Abstract Study question Is aspiration of more oocytes than the antral follicle count (AFC) beneficial for the current (pregnancy/live birth rates) and future products of an ART cycle? Summary answer Aspirating more oocytes than the AFC does not influence the outcome of the fresh cycle but is beneficial for fertility preservation and cumulative pregnancy rates. What is known already AFC is a reliable and immediate indicator for ovarian reserve assessment and is in correlation with the ovarian response to gonadotropin stimulation. Additionally, correlation between AFC and embryo quality, clinical pregnancy and live birth rates was reported. There is no data concerning the impact of the ratio between the AFC and actual number of oocytes retrieved on cycle outcome. Study design, size, duration Data of the first oocyte aspiration for ICSI performed between 2018-2022 in attempt to conceive (ICSI, n = 399) or for planned oocyte vitrification (fertility preservation FP, n = 283) was retrieved. Each group was divided into two subgroups according to their ‘oocyte/AFC index’ (OAFCI): &amp;lt;1 and ≥1. The stimulation parameters, number of aspirated oocytes, their maturity rate, number of cryopreserved oocytes/embryos, clinical pregnancy (CPR) and live birth rates (LBR) were compared between the subgroups. Participants/materials, setting, methods The AFC was determined by professional sonographers using a 9 MHz transvaginal ultrasound probe. The most adjacent measurement to the stimulation initiation was used. Stimulation protocol and FSH dose were determined according to the AFC and individual clinical consideration. Patients not in their first cycle, natural cycle aspirations, and cases in which no oocytes were retrieved, were excluded. Main results and the role of chance OAFC≥1 was associated with higher pre-trigger estradiol (6159 pmol/L vs. 4304, p &amp;lt; 0.001 for ICSI, 4949 vs. 3488, p &amp;lt; 0.001 for FP), and longer duration of simulation (9.8 days vs. 9, p &amp;lt; 0.001 for both FP and ICSI). More oocytes were aspirated in OAFC≥1 groups in both FP (16.9±11.2 vs. 7.9±5.9, p &amp;lt; 0.001) and ICSI (17.4±9.8 vs. 10.7±6.7, p &amp;lt; 0.001). Oocyte maturity was unaffected by the OAFCI in the ICSI group, but was lower in FP group at OAFC≥1 (0.79 vs.0.84 p = 0.005). OAFCI≥1 was associated with a higher number of cryopreserved embryos (3.9 vs. 2.3, p &amp;lt; 0.001 for ICSI) and a higher number of vitrified oocytes (13.4 vs. 6.4 p &amp;lt; 0.001 for FP). The OAFCI had no impact on CPR (39% vs. 60%, p = 0.27) and LBR (19.9% vs. 24.8%, p = 0.33). On multivariate analysis controlling for age, gonadotropin dosage and duration of stimulation, OAFC≥1 was associated with a higher number of cryopreserved embryos (ICSI group aOR 1.2, 95% CI 1.1-1.3, p &amp;lt; 0.001), and vitrified oocytes (aOR 1.2, 95% CI 1.1-1.2, p &amp;lt; 0.001) and lower maturity index (aOR 0.1, 95% CI 0.03-0.51, p &amp;lt; 0.001) in the FP group. Limitations, reasons for caution Retrospective study analyzing results of treatment cycles without an intention to aspirate differently. Wider implications of the findings Aspiration of a more oocytes than the current AFC was not associated with higher CPR or LBR in the fresh cycle, but harbors the possibility to cryopreserve more oocytes and embryos. This might translate into higher cumulative pregnancy rates later on. Trial registration number Not applicable

O-195 Decreased embryo developmental potential and lower cumulative pregnancy rate in males with multiple morphological abnormalities of the sperm flagella

Abstract Study question Is there any association between the multiple morphological abnormalities of the sperm flagella (MMAF) patients and the comprehensive outcomes of assisted reproductive technology (ART) cycles? Summary answer Patients with MMAF presented compromised ART outcomes, including lower embryo developmental potential and impaired clinical outcomes, compared with the cohort of oligoasthenospermia. What is known already Several studies have reported a positive intracytoplasmic sperm injection (ICSI) outcome in the MMAF cohort, and others have opposite opinions. The association between MMAF and ART outcomes is still controversial and open for debate. Furthermore, the neonatal outcomes and the information regarding the mutations of MMAF patients were incomplete. Study design, size, duration A retrospective cohort study of MMAF patients was performed at a reproductive medicine center in China between January 2014 and July 2022. Participants/materials, setting, methods Thirty-eight MMAF individuals were recruited based on a typical MMAF phenotype (abnormal sperm flagella, including short, absent, coiled, bent, and/or irregular flagella) and 131 couples with male infertility undergoing in vitro fertilization (IVF)/ICSI treatments over the same period were included as the control pool. Whole exome sequencing (WES) was performed to confirm the genetic pathogenesis of MMAF. Main results and the role of chance Pathogenic variants in known genes of DNAH1, DNAH11, CFAP43, FSIP2, and SPEF2 were identified in MMAF patients. The ART outcomes, including the fertilization rate, 2PN cleavage rate, blastocyst formation rate, and available blastocyte rate, were all significantly lower in the MMAF group than those in the control group (P&amp;lt;0.05). Moreover, the CLPR in the MMAF group was lower than that in the control group according to the embryo transfer times (68.6% vs. 86.5%, P=0.033) and complete cycles (66.7% vs. 84.2%, P=0.020), while no significant differences were found in the neonatal outcomes. Limitations, reasons for caution The sample size was limited due to the low incidence of MMAF and WES was not performed in all MMAF patients. Further exploration of the potential genetic mutations or underlying mechanisms in patients without identified mutations was needed. Moreover, long-term follow-up of neonates needs to be addressed in the future. Wider implications of the findings The current study identified the causative genetic mutations which were partly obligated to the pathogenesis of MMAF and presented the relationship between MMAF and compromised ART outcomes. These results may provide evidence support for clinicians in genetic counseling and clinical instruction in specific MMAF patients. Trial registration number the National Key Research &amp; Development Program of China (2021YFC2700603)

P-541 First live birth report of identical twins from a single low-grade mosaic blastocyst (46,XY/45,XY,-19) transfer: when a small chance becomes a double miracle

Abstract Study question N/A Summary answer First live birth report of identical twins from the transfer of a single low-grade mosaic blastocyst for monosomy on chromosome 19. What is known already The clinical decision-making in cases involving the transfer of low-grade mosaic embryos remains controversial. Recent studies have indicated that low-grade mosaic embryos exhibit pregnancy rates similar to euploid embryos, encouraging their transfer. However, the judgment to proceed in most cases is still challenging. The transfer of a low-grade mosaic embryo for monosomy on chromosome 19 is considered relative safe. The occurrence of human twins resulting from embryo splitting in ART (Assisted Reproductive Technology) cycles is a rare phenomenon. To date, there are no reports of the birth of identical twins from a single low-grade mosaic embryo transfer. Study design, size, duration This is a single-case report detailing an assisted reproduction cycle conducted by a couple. Participants/materials, setting, methods A couple with a nine-year history of infertility, characterized by low ovarian reserve and azoospermia, underwent an ICSI (Intracytoplasmic Sperm Injection) cycle in October 2022. Due to azoospermia, microsurgical epididymal sperm aspiration and subsequent freezing of the retrieved sperm were performed prior to ovum pick-up. PGT-A (Preimplantation Genetic Testing for Aneuploidy) of the resultant blastocysts was conducted, followed by the transfer of a single low-grade mosaic after a modified natural endometrial preparation cycle. Main results and the role of chance Seven mature oocytes were retrieved, and following ICSI with the thawed seminal sample, four blastocysts were developed and biopsied for PGT-A analysis. Out of these four high-quality blastocysts, three were aneuploid, and the remaining one was a low-grade (50%) mosaic for monosomy on chromosome 19. After genetic counselling, the patients decided to proceed with the transfer of a day 5 3AA low-grade mosaic embryo, which led to a successful pregnancy. The transferred embryo split, generating a pregnancy of identical twins. The twins were delivered via cesarean section at 30 weeks and 5 days of gestational age. The premature delivery was necessitated due to the mother developing cardiac insufficiency related to pre-existing valvulopathy and a superimposed venous thromboembolism. Peripheral blood samples from the twins have been collected for a 100-cell karyotype analysis (results will be available by February 9th). This case marks the first reported instance of twins born from the transfer of a single low-grade mosaic blastocyst (46,XY/45,XY,-19). Limitations, reasons for caution This is a retrospective case-report from one couple, describing a rare event. Wider implications of the findings This case-report could elucidate the physician’s decision and slightly encourage the transfer of low-grade mosaic embryos when there are no full euploids available. Trial registration number Not pllicable

O-080 The effect of psychosocial support on motivation for assisted reproductive treatments

Abstract Study question Does psychosocial intervention targeting better psychological adjustment increase the likelihood of treatment continuation among women pursuing assisted reproductive technologies (ART)? Summary answer After a psychosocial intervention, a robust amelioration occurred in distress levels, yet no notable change was detected in motivational levels for treatment continuation. What is known already Approximately 20% of patients stop ART treatments prematurely, often after three unsuccessful cycles, even in countries with a public funding of ART, despite a 15% success rate increase per recommended cycle. Emotional distress, poor prognosis, and financial burden are risk factors for early cessation. Since depression has been shown to predict ART discontinuation, it is logical to expect that an alleviation of depression is accompanied by a strengthening of the intention for treatment continuation. Study design, size, duration A prospective, pre-post design, single-centre, interventional cohort study was performed between December, 2019 and October, 2022 (start and end of recruitment, respectively). 2636 patients were approached for study purposes, 610 were assessed for eligibility, and 168 were included in the intervention. With a 8.3% attrition rate, data of 154 patients were analysed in this study, originally a randomized controlled trial, whose data were pooled for the present purposes. Participants/materials, setting, methods Women scoring in mild-to-moderate impairment ranges on four psychological tests were invited to take part in a 10-week, 135-minute/week intervention at the assisted reproduction centre of a large university hospital. Psychological data were collected pre- and post-intervention, alongside demographic and fertility specifics. Perceived probability of treatment continuation in the event of an unsuccessful ART cycle was assessed with a Likert-scale single question at both time points. Multivariate linear models were utilized for statistical analysis. Main results and the role of chance In comparison with baseline values, significant changes in the expected direction occurred in depressive symptoms, anxiety values, infertility-specific stress and fertility-related quality of life (t-values ranging from 6.559 to 7.949; all p-values&amp;lt;0.001). However, neither treatment-related quality of life (t = 0.718; p = 0.474), nor motivational levels for treatment continuation changed significantly (t = 1.058; p = 0.292). Age, however, had a significant main effect on perceived probability of treatment continuation (t = 2.864; p = 0.004). Limitations, reasons for caution Limitations include potential inter-group differences, unmeasured motivational factors, and no male partner data. Biological factors other than age, aetiology and duration of infertility may have confounded study results. Another limitation is the lack of long-term follow-up, given that perceived probability of treatment continuation may not coincide with actual behaviour. Wider implications of the findings Psychosocial interventions are efficient in alleviating distress but these improvements may not directly impact motivational changes. Biological factors such as age may have a more accentuated effect on ART treatment continuation than psychological aspects. Alternative hypotheses on precise determinants and modifiable factors influencing motivation need testing. Trial registration number Not applicable

P-394 Using machine learning to predict the risk of miscarriage in infertile couples undergoing assisted reproductive cycles

Abstract Study question Can an artificial intelligence (AI)-based model predict chemical abortion using basic clinical data of infertile couples undergoing assisted reproductive technology (ART)? Summary answer We have combined basic clinical data and machine learning algorithms to create a noninvasive AI model for prediction of chemical abortion. What is known already Approximately 10 to 15 percent of natural pregnancies encounter the issue of abortion, it significantly gets worse in pregnancies resulting from assisted reproductive methods. The emotional burden on infertile couples during their self-belief therapy journey is substantial. Predicting treatment outcomes can significantly decrease the anxiety experienced by these couples. This research aims to develop a machine learning-based model for predicting chemical abortion in infertile women who have conceived through assisted reproductive methods, offering an initial assessment. Study design, size, duration This study involved analysis of retrospectively collected records including basic clinical data and pregnancy outcomes of 1234 records between March 2020 and August 2022. It designs in two fundamental phases: data extraction and model implementation. The extracted data from the study group was evaluated with registered physical and electronic records to validate and correct the information. Participants/materials, setting, methods This study was conducted at Yazd Reproductive Sciences Institute, Yazd, Iran. Data pre-processing was performed for data mining and model implementation. This process yielded a dataset of 1234 samples containing 32 selected variables. Machine learning algorithms, including decision tree, random forest, logistic regression, and support vector machine, were employed for models’ assessment. Regarding the imbalance nature of the gathered dataset, balancing techniques were performed to enhance model performance. Balancing was applied using SMOTE, ADYNS algorithms. Main results and the role of chance Evaluation of the above-mentioned models across unbalanced, balanced, and reduced datasets revealed the random forest model as the most robust choice, achieving accuracies of 79.80%, 88.90%, and 89.90% in the respective test phases. In terms of balancing process, ADYNS was superior to SMOTE. In addition, this research identified 18 influential variables for predicting abortion. Limitations, reasons for caution This investigation was performed using retrospective data; some incomplete records were excluded. In addition, the data heterogenicity may affect the analysis. The model developed is limited to the analysis of basic clinical data, further modification of the model is needed to incorporate information from different stages of the ART cycle. Wider implications of the findings This study demonstrated a model to predict chemical miscarriage. The high accuracy of this model showed that this model could be implemented in ART clinics as a primary tool to assist clinicians in making an accurate initial judgment on the condition of patients with infertility and history of pregnancy loss. Trial registration number not applicable