Miscarriage Rate Research Articles

Effect of different treatment protocols on in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) outcomes in adenomyosis women: a systematic review and meta-analysis

ObjectivesPregnancy outcomes of different ovarian stimulation protocols for in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) in patients with adenomyosis are not explicit. This meta-analysis aimed to systematically evaluate the effects of...

The significance of delivery methods and fetal gender in reducing stillbirth rate: Using the generalized regression model

AimDespite stillbirth being a significant burden for maternal lives, families, and communities worldwide, it is often neglected and overlooked in many countries. The fetal gender and the delivery method are two interaction factors that directly impact the stillbirth rate. This study aimed to identify the impact of fetal gender on stillbirth delivery methods, either cesarean section or vaginal delivery. MethodThe current research analyzed the stillbirths recorded over ten years between January 1st, 2008, and December 31st, 2017, obtained from the Maternity Teaching Hospital in Erbil City, the capital of the Kurdistan Region of Iraq. ResultsThe results showed that stillbirths remain a significant public health concern in the region, with 11.7 stillbirths occurring for every 1000 deliveries. The generalized regression model for each normal, beta, and gamma distribution was used to determine the best fit of the data. The study found that for fetal males, vaginal delivery reduced the stillbirth rate by 4.2 % and the cesarean section rate by 3.6 % while for fetal females, vaginal delivery reduced the stillbirth rate by 4.7 % and the cesarean section rate by 6 %. ConclusionThe findings suggest that healthcare in the region should prioritize reducing the incidence of stillbirths during pregnancy and delivery, considering factors such as fetal gender and delivery mode.

First-line infertility treatment in normal or subnormal sperm: Interest of a simplified pre-IMSI test.

In the field of male infertility, when sperm is normal/subnormal, a few "add-on" routine tests can complete the basic semen examination. The aim of this study was to develop and evaluate a faster, simplified motile sperm organelle morphology examination (MSOME) technique for selected infertile patients with apparently normal/subnormal sperm and, in their background: failure of two or three intrauterine insemination (IUI) cycles, repeatedly fragmented embryos, embryonic development to blastocyst-stage failures, repeated miscarriages, a long period of infertility or 2 or more IVF attempts without pregnancy. Our test results were correlated with IUI, conventional in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) and intracytoplasmic morphologically selected sperm injection (IMSI) outcomes. We validated an adapted version of the MSOME analysis called the pre-IMSI test (PIT), based on vacuole evaluation alone. 248 infertile patients from our assisted reproductive technology (ART) Center were retrospectively selected and split into three PIT score subgroups (patients with ≤8% (score I), 9 to 15% (score II) and ≥16% normal spermatozoa (score III)) based on the correlation between PIT results and each ART technique outcome. The choice of one or another of these ART techniques had been made according to the usual clinico-biological criteria. Clinical outcomes for each of the three PIT subgroups were compared individually for the different ART techniques. For ICSI, the effect of the PIT score subgroup was significant for clinical pregnancies (p = 0.0054) and presented a trend for live births (p = 0.0614). Miscarriage rates of IVF attempts were statistically different depending on the PIT score (p = 0.0348). Furthermore, the odds ratios of clinical pregnancy rates were significantly different according to PIT score subgroup when comparing ICSI vs. IMSI or IVF vs. ICSI attempts. IMSI appears to be recommended when sperm belongs to PIT score I, ICSI when it belongs to PIT score II and IVF or IUI when sperm is of PIT score III quality in selected infertile couples. The lack of statistical power in these PIT subgroups means that we must remain cautious in interpreting results. Our results support the interest of this simplified test for certain couples with normal/subnormal sperm to help choose the most efficient ART technique, even as first-line treatment.

Maternal and fetal outcomes of antiepileptic treatments during pregnancy: A retrospective study

IntroductionEpilepsy is a disease that affects a significant proportion of the female population worldwide. The management of anti-seizure medications during pregnancy and the potential adverse outcomes to both the mother and fetus represent a significant challenge. This retrospective study aimed to evaluate the impact of anti-seizure medications during pregnancy by comparing maternal and fetal outcomes between pregnant women with and without epilepsy. MethodsA total of 242 participants were analysed, including 112 with epilepsy and 130 healthy pregnant controls. Maternal age, medical history, seizure characteristics, use of anti-seizure medications, and pregnancy history were recorded. Maternal and fetal complications, delivery modes, and perinatal outcomes were evaluated. ResultsA total of 242 patients, including 112 (46.3 %) pregnant women with epilepsy and 130 (53.7 %) healthy pregnant women, were included in the study. Among pregnant patients with epilepsy, 4 (3.5 %) did not use anti-seizure medications, 79 (70.5 %) received monotherapy, and 29 (25.8 %) received polytherapy. The rates of pregnancy termination, spontaneous abortion, and maternal and fetal complications were significantly higher in pregnant women with epilepsy (p = 0.045, p = 0.045, p < 0.001, and p = 0.016, respectively). Folic acid use, planned pregnancy rate and postpartum breastfeeding rate were all statistically lower in pregnant women with epilepsy (p < 0.001, p < 0.001, p < 0.001, respectively). The rates of intensive care unit stay, infants with birth weight less than 2500 g, congenital malformations, and preterm births were significantly higher in babies born to pregnant women with epilepsy (p < 0.001, p = 0.047, p = 0.003, and p = 0.051, respectively). Gestational diabetes mellitus was observed in 4 (13.8 %) and congenital malformations in 4 (14.3 %) of the pregnant women with epilepsy who received polytherapy, and in both cases these rates were statistically higher than those of pregnant women with epilepsy who received monotherapy (p = 0.048 and p = 0.004, respectively). DiscussionThis study demonstrated that pregnancies among women affected by epilepsy have significantly higher rates of maternal and fetal complications, spontaneous abortions, and premature births. Polytherapy with anti-seizure medications is associated with an increased risk of gestational diabetes and congenital anomalies. Notably, folic acid use, planned pregnancy, and postpartum breastfeeding were less common in patients with epilepsy. The most commonly prescribed anti-seizure medications were levetiracetam and lamotrigine. Caesarean section is a common mode of delivery in pregnancies of mothers with epilepsy. ConclusionThese results suggest that epilepsy increases both maternal and fetal complications during pregnancy. Furthermore, the use of anti-seizure medications appears to have a significant impact on pregnancy outcomes. Our findings highlight the need for comprehensive management strategies and informed decision making to reduce risks and optimise maternal and fetal outcomes among women with epilepsy.

High Rates of Miscarriage and Stillbirth among Pregnant Women with Clade I Mpox (Monkeypox) Are Confirmed during 2023-2024 DR Congo Outbreak in South Kivu Province.

Mpox (monkeypox) is a neglected tropical disease that has received increased attention since the multi-nation outbreak that began in 2022. The virus is endemic in West and Central Africa, where the Democratic Republic of the Congo (DRC) is the most affected country. Clade I monkeypox virus (MPXV) infection is endemic in the DRC and has an overall case fatality rate of 10.6% among children and adults. A study conducted in Sankuru Province, DRC, from 2007 to 2011 demonstrated that 75% of pregnant women with mpox had miscarriages or stillbirth. Further analysis of a stillborn fetus showed that MPXV could infect both the placenta and fetus, causing congenital infection. No additional cases of Clade I MPXV in pregnant women were reported until a new outbreak occurred in South Kivu Province during 2023 and 2024. Eight pregnant women having Clade I MPXV infection were identified, of whom four had either miscarriages or stillbirth, representing a 50% fetal mortality rate. These reports confirm previous data from the DRC that indicate the capability of Clade I MPXV to affect the fetus, causing congenital infection and fetal loss in a high percentage of cases. In this article, we review both past and new data from the DRC on the effects of Clade I MPXV during pregnancy and discuss the association of mpox with fetal loss.

COVID-19 infection during pregnancy and risk of early and late spontaneous miscarriages: A matched case-control population-based study.

To evaluate the effect of COVID-19 during the first trimester on the rate of first- and second-trimester miscarriages. Secondary aims include the effect on stillbirths and the correlation between symptom severity and pregnancy outcomes. A retrospective matched case-control population-based study extracted data from electronic medical records of a nationwide database of the second largest healthcare organization that provides medical services to over 2 000 000 patients in Israel. Pregnancy outcomes in COVID-19-positive pregnant patients in 2020 were compared with an age- and gestational-week-matched 1:2 case-control cohort of pre-pandemic pregnant patients that received medical care in 2019. Of 68 485 pregnant women treated in 2020, 2333 were COVID-19-positive during pregnancy: 215 during the first trimester, 791 during the second trimester, and 1327 during the third trimester. We compared these data with the control cohort of 4580 pre-pandemic pregnant patients. The rate of spontaneous miscarriage was significantly higher 146/2187 (6.3%) in COVID-19-positive patients versus 214/4580 (4.7%), (P < 0.01, odds ratio 1.34, 95% confidence interval 1.094-1.691). Most miscarriages occurred during the first trimester in both groups, yet the rates were significantly higher in the study group (5.4% vs 3.8%, P < 0.01). There was no association between COVID-19 severity and miscarriage risk. COVID-19 diagnosis during early pregnancy increased the rate of spontaneous miscarriage in our cohort compared with an age- and gestational-week-matched pre-pandemic control group.

Improvement of early miscarriage rates in women with adenomyosis via oxytocin receptor antagonist during frozen embryo transfer-a propensity score-matched study

BackgroundDysfunctional uterine peristalsis seems to play a pivotal role in hindering embryo implantation among women diagnosed with adenomyosis. This research aims to investigate whether administering an oxytocin receptor antagonist during a frozen embryo transfer (FET) cycle using a hormone replacement therapy (HRT) protocol can enhance in vitro fertilization (IVF) outcomes for infertile women affected by adenomyosis.MethodsBetween January 2018 and June 2022, our reproductive center conducted IVF-FET HRT cycles for infertile women diagnosed with adenomyosis. Propensity score matching was employed to select matched subjects between the two groups in a 1:1 ratio. Following this, 168 women received an oxytocin receptor antagonist during FET, constituting the study group, while the matched 168 women underwent FET without this antagonist, forming the control group. We conducted comparative analyses of baseline and cycle characteristics between the two groups, along with additional subgroup analyses.ResultsThe study group exhibited notably lower rates of early miscarriage compared to the control group, although there were no significant differences in clinical pregnancy rates, ongoing pregnancy rates, and live birth rates between the two groups. Multivariate analysis revealed a negative correlation between the use of oxytocin receptor antagonists and early miscarriage rates in women with adenomyosis. Subgroup analyses, categorized by age, infertility types, and embryo transfer day, showed a substantial decrease in early miscarriage rates within specific subgroups: women aged ≥ 37 years, those with secondary infertility, and individuals undergoing day 3 embryo transfers in the study group compared to the control group. Furthermore, subgroup analysis based on adenomyosis types indicated significantly higher clinical pregnancy rates, ongoing pregnancy rates and live birth rates in the study group compared to the control group among women with diffuse adenomyosis.ConclusionsAdministering an oxytocin receptor antagonist during FET may reduce the early miscarriage rates in women with adenomyosis.

Stillbirth risk by fetal size among 126.5 million births in 15 countries from 2000 to 2020: A fetuses-at-risk approach.

To compare stillbirth rates and risks for small for gestational age (SGA), large for gestational age (LGA) and appropriate for gestational age (AGA) pregnancies at 24-44 completed weeks of gestation using a birth-based and fetuses-at-risk approachs. Population-based, multi-country study. National data systems in 15 high- and middle-income countries. Live births and stillbirths. A total of 151 country-years of data, including 126 543 070 births across 15 countries from 2000 to 2020, were compiled. Births were categorised into SGA, AGA and LGA using INTERGROWTH-21st standards. Gestation-specific stillbirth rates, with total births as the denominator, and gestation-specific stillbirth risks, with fetuses still in utero as the denominator, were calculated from 24 to 44 weeks of gestation. Gestation-specific stillbirth rates and risks according to size at birth. The overall stillbirth rate was 4.22 per 1000 total births (95% CI 4.22-4.23) across all gestations. Applying the birth-based approach, the stillbirth rates were highest at 24 weeks of gestation, with 621.6 per 1000 total births (95% CI 620.9-622.2) for SGA pregnancies, 298.4 per 1000 total births (95% CI 298.1-298.7) for AGA pregnancies and 338.5 per 1000 total births (95% CI 337.9-339.0) for LGA pregnancies. Applying the fetuses-at-risk approach, the gestation-specific stillbirth risk was highest for SGA pregnancies (1.3-1.4 per 1000 fetuses at risk) prior to 29 weeks of gestation. The risk remained stable between 30 and 34 weeks of gestation, and then increased gradually from 35 weeks of gestation to the highest rate of 8.4 per 1000 fetuses at risk (95% CI 8.3-8.4) at ≥42 weeks of gestation. The stillbirth risk ratio (RR) was consistently high for SGA compared with AGA pregnancies, with the highest RR observed at ≥42 weeks of gestation (RR 9.2, 95% CI 15.2-13.2), and with the lowest RR observed at 24 weeks of gestation (RR 3.1, 95% CI 1.9-4.3). The stillbirth RR was also consistently high for SGA compared with AGA pregnancies across all countries, with national variability ranging from RR 0.70 (95% CI 0.43-0.97) in Mexico to RR 8.6 (95% CI 8.1-9.1) in Uruguay. No increased risk for LGA pregnancies was observed. Small for gestational age (SGA) was strongly associated with stillbirth risk in this study based on high-quality data from high- and middle-income countries. The highest RRs were seen in preterm gestations, with two-thirds of the stillbirths born as preterm births. To advance our understanding of stillbirth, further analyses should be conducted using high-quality data sets from low-income settings, particularly those with relatively high rates of SGA.

Assessing vaginal microbiome through Vaginal Microecology Evaluation System as a predictor for in vitro fertilization outcomes: a retrospective study.

This study aims to evaluate the effectiveness of the Vaginal Microecology Evaluation System (VMES) in assessing the dynamics of the vaginal microbiome (VM) throughout the process of in vitro fertilization and embryo transfer (IVF-ET). Furthermore, it seeks to explore the potential correlation between distinct types of VM ecology and the success rate of IVF-ET. This study employed VMES to ascertain the composition of the VM. Data were collected from infertile women who underwent their initial IVF-ET treatment for tubal factor between January 2018 and December 2021. A retrospective analysis of pregnancy outcomes resulting from their fresh embryo transfer was conducted to determine the predictive significance of the vaginal microenvironment. We demonstrate that VMES is able to predict IVF-ET outcomes in patients diagnosed with Bacterial Vaginosis (BV). Notably, a discernible shift in the VM was observed in a decent subset of patients following Controlled Ovarian Stimulation (COS), though this phenomenon was not universal across all participants. Specifically, there was a noteworthy increase in the proportion of patients exhibiting BV and uncharacterized dysbiosis subsequent to COS. Furthermore, our investigation revealed a significant correlation between VM and both the live birth rate and early miscarriage rate. Employing a multivariable logistic regression model, we identified that VM status pre-COS, VM status post-COS, patient age, and the number of embryos transferred emerged as independent predictors of the live birth rate. Our study suggests that, during IVF-ET treatment, the VMES can effectively detect changes in the VM, which are strongly correlated with the pregnancy outcome of IVF-ET procedures.

Meta-analysis of intrauterine hCG perfusion efficacy in recurrent implantation failure as defined by ESHRE guidelines

PurposeThis study evaluates the efficacy of intrauterine hCG perfusion for RIF, as defined by ESHRE 2023 guidelines, highlighting hCG as a cost-effective alternative to other immunotherapies, especially suitable for less developed regions. It aims to clarify treatment guidance amidst previous inconsistencies.MethodsThis meta-analysis, registered with PROSPERO (CRD42024443241) and adhering to PRISMA guidelines, assessed the efficacy and safety of intrauterine hCG perfusion in enhancing implantation and pregnancy outcomes in RIF. Comprehensive literature searches were conducted through December 2023 in major databases including PubMed, Web of Science, Embase, the Cochrane Library, and key Chinese databases, without language restrictions. Inclusion and exclusion criteria were strictly aligned with the 2023 ESHRE recommendations, with exclusions for studies lacking robust control, clear outcomes, or adequate data integrity. The risk of bias was evaluated using the Newcastle-Ottawa Scale, ROBINS-I, and RoB2 tools. Data analysis was performed in R using the ‘meta’ package, employing both fixed and random effect models to account for study variability. Subgroup analyses by dosage, volume, hCG concentration, timing of administration, and type of embryo transfer were conducted to deepen insights, enhancing the reliability and depth of the meta-analysis in elucidating the role of hCG perfusion in RIF treatments.ResultsData from 13 studies, comprising six retrospective and six prospective studies from single centers, along with one multi-center RCT, totaling 2,157 participants, were synthesized to evaluate the effectiveness of intrauterine hCG perfusion in enhancing implantation and pregnancy outcomes in patients with RIF. Significant improvements were observed in clinical pregnancy and embryo implantation rates across various dosages, timing of administration, and embryo developmental stages, without impacting miscarriage rates. Notably, the most significant efficacy within subgroups occurred with a 500 IU dosage and perfusion parameters of ≤ 500µL volume and ≥ 2 IU/µL concentration. Additionally, a limited number of studies showed no significant increases in ectopic pregnancy or multiple pregnancy rates, and a modest improvement in live birth rates, although the small number of these studies precludes definitive conclusions.ConclusionsThe analysis suggests that intrauterine hCG perfusion probably enhances embryo implantation, clinical pregnancy, and live birth rates slightly in RIF patients. Benefits are indicated with a dosage of 500 IU and a maximum volume of 500µL at concentrations of at least 2 IU/µL. However, substantial heterogeneity from varying study types and the limited number of studies necessitate cautious interpretation. These findings underscore the need for more rigorously designed RCTs to definitively assess the efficacy and safety.

Standardizing Fetal Movement Monitoring using Count the Kicks.

Stillbirth affects 1 in 175 pregnancies in the United States. There are significant racial and ethnic disparities in rates of stillbirth. Rates of stillbirth are highest among non-Hispanic Native Hawaiian or Other Pacific Islander and non-Hispanic Black women, more than twice the rate of non-Hispanic White women. Stillbirth is a public health crisis that warrants attention as it has significant physical, psychosocial, and economic effects on women and their family. Many stillbirths occur due to placental insufficiency, causing a lack of oxygenation of the fetus, which can result in decreased movement. Pregnant patients who experience stillbirth often observe decreased fetal movement days before birth. Daily fetal movement monitoring has the potential to identify pregnancies at risk so providers can intervene. Count the Kicks is a fetal movement monitoring program that provides standardized education and resources for expectant parents. Increased awareness of providers and childbearing families about the importance of fetal movement monitoring, standardized provision of education on fetal movement counting, and what to do if a baby's normal movement patterns change can be helpful in promoting healthy pregnancy outcomes.

Hysteroscopic Management of Symptomatic Cesarean Scar Diverticulum in Patients Undergoing Frozen-Thawed Embryo Transfer: Impact on Clinical Pregnancy Rates and Pregnancy Complications.

This retrospective cohort study aimed to compare the clinical outcomes of patients with cesarean scar defect (CSD) undergoing frozen embryo transfer (FET) with or without hysteroscopic repair surgery. The study included 82 patients, with 48 patients in surgical group A (undergoing CSD repair) and 34 patients in surgical group B (undergoing hysteroscopic treatment for other uterine lesions). The results showed that patients in group A had a larger CSD volume and a different shape compared to group B. However, there was no significant difference in clinical pregnancy rates between the two groups. Additionally, there were no differences in miscarriage, live birth, or preterm birth rates, and no complications such as scar pregnancy or placental abnormalities were observed in either group. These findings suggest that hysteroscopic treatment of CSD in symptomatic patients undergoing FET does not increase the risk of pregnancy complications and can lead to comparable clinical pregnancy rates with asymptomatic patients. Further studies with larger sample sizes are needed to confirm these results and evaluate long-term reproductive outcomes following CSD repair.

Amnioinfusion compared with expectant management in oligohydramnios with intact amnions in the second and early third trimesters.

Treatment of oligohydramnios in the mid-trimester is challenging, because of the high incidence of adverse perinatal outcomes mainly due to bronchopulmonary dysplasia. Antenatal amnioinfusion has been proposed as a possible treatment for oligohydramnios with intact amnions, but there are few relevant studies. This study aimed to evaluate the effectiveness of transabdominal amnioinfusion in the management of oligohydramnios without fetal lethal malformations in the second and early third trimesters. It is a historical cohort study. A total of 79 patients diagnosed with oligohydramnios at 18-32 weeks gestation were enrolled. In the amnioinfusion group (n = 39), patients received transabdominal amnioinfusion with the assistance of real-time ultrasound guidance. In the expectant group (n = 41), patients were treated with 3000 mL of intravenous isotonic fluids daily. The perioperative complications and perinatal outcomes were analyzed. Compared with the expectant group, the delivery latency was significantly prolonged, and the rate of cesarean delivery was significantly reduced in the amnioinfusion group (p < 0.05). Although the rate of intrauterine fetal death was significantly reduced, the incidence of spontaneous miscarriage, premature rupture of membranes (PROMs), and threatened preterm labor were significantly higher in the amnioinfusion group than in the expectant group (p < 0.05). There was no significant difference in terms of perinatal mortality (28.9% vs. 41.4%, p > 0.05). Multivariate logistic regression revealed that amnioinfusion (odds ratio [OR] 0.162, 95% confidence interval [CI] 0.04-0.61, p = 0.008) and gestational age at diagnosis (OR 0.185, 95% CI 0.04-0.73, p = 0.016) were independently associated with neonatal adverse outcomes. Further subgrouping showed that amnioinfusion significantly reduced the frequency of bronchopulmonary hypoplasia for patients ≤26 weeks (26.7% vs. 75.0%, p = 0.021). The rates of other neonatal complications were similar in both groups. Amnioinfusion has no significant effect on improving the perinatal mortality of oligohydramnios in the second and early third trimesters. It may lead to a relatively high rate of PROM and spontaneous abortion. However, amnioinfusion may significantly improve the latency period, the rate of cesarean delivery, and neonatal outcomes of oligohydramnios, especially for women ≤26 weeks with high risk of neonatal bronchopulmonary hypoplasia.

Effects of high-normal fasting blood glucose on ART outcomes of frozen-thawed single blastocyst transfer in women with normal BMI.

This retrospective cohort study aims to investigate whether high-normal fasting blood glucose (FBG) affects assisted reproductive technology (ART) outcomes undergoing single blastocyst frozen-thawed embryo transfer (FET) cycles in women with normal body mass index (BMI). 944 women with normal BMI and FBG levels undergoing single blastocyst FET cycles were enrolled. Based on the median of FBG (4.97mmol/L, 1mmol/L = 18mg/dL), the subjects were categorized into the low-normal group (3.90 ≤ FBG ≤ 4.97 mmol/L, n = 472) and the high-normal group (4.97 < FBG < 6.10mmol/L, n = 472). Multivariable logistic regression and receiver operating characteristic (ROC) were used to analyze the relationship between high-normal FBG and ART outcomes. live birth rate (LBR). LBR was significantly lower in the high-normal group than in the low-normal group (36.8% vs. 45.1%, p = 0.010), and the miscarriage rate was considerably higher than that in the low-normal group (23.9% vs. 16.5%, p = 0.041). High-normal FBG of female was an independent predictor of live birth (adjusted OR:0.747, 95% CI: 0.541-0.963, p = 0.027) and miscarriage (adjusted OR:1.610, 95% CI: 1.018-2.547, p = 0.042). ROC analyses showed that the cut-off values of FBG (endpoints: live birth and miscarriage) were 5.07mmol/L, and 5.01mmol/L, respectively. In women with normal BMI, high-normal FBG is an independent risk factor for lower LBR and higher miscarriage rate in single blastocyst FET cycles. Attention to preconception FBG monitoring in this particular population may allow early intervention to improve ART outcomes.

P-151 Investigation of pregnancy outcomes for blastocysts with microcellular leakage of trophectoderm or inner cell mass from ICSI-induced zona pellucida microslits

Abstract Study question How does ICSI-induced leakage of trophectoderm (TE) or inner cell mass (ICM) from microslits in the zona pellucida (ZP) affect pregnancy outcomes following blastocyst transfer? Summary answer Microcellular leakage of TE and ICM did not affect pregnancy outcome, but blastocysts with ICM leakage above 53.6% had a lower pregnancy rate. What is known already The leakage of TE cells through the ZP (trophectoderm vesicles; TV) has been reported to be more common in ICSI than in conventional IVF, caused by the opening of the ZP with microslits for ICSI. This phenomenon may be improved through the implementation of assisted hatching during transplantation, however, there are few reports investigating its impact on pregnancy.Furthermore, there are no reports on the impact of inner cell mass leakage (inner cell mass vesicles; IV) on pregnancy outcomes, and it is unclear what level of ICM leakage is acceptable for transplantation. Study design, size, duration In this retrospective study, we analyzed clinical medical reports at the Takahashi Women’s Clinic in Japan. A total of 551 patients (1093 blastocysts) who underwent freeze-thaw single blastocyst transfer with laser assisted hatching between January 2019 and October 2023 were included. Blastocysts used for transfer were 2PN embryos obtained by PIEZO-ICSI and cultured in a time-lapse incubator (EmbryoScope+). Participants/materials, setting, methods The blastocysts were classified into control (N = 682), TV (N = 377), and IV groups (N = 34). Pregnancy outcomes were compared using logistic regression analysis, considering patient age, blastocyst grade (Gardner criteria), culture days, BMI, and basal AMH. Bonferroni correction was used for multiplicity correction, considering P &amp;lt; 0.0167 as significant. The ICM leakage rate (%) was calculated as: (leaked ICM area/ICM area before leakage) × 100. Pregnancy cutoff was determined by ROC analysis. Main results and the role of chance The hatching rates for the control, TV, and IV groups were 69.6% (475/682), 78.8% (297/377), and 82.4% (28/34), respectively. Pregnancy rates (fetal heartbeat) were 44.6% (304/682), 57.0% (215/377), and 50.0% (17/34), respectively, and miscarriage rates were 26.3% (80/304), 26.0% (56/215), and 23.5% (4/17), respectively. Logistic regression analysis considering patient background showed no significant differences in hatching, pregnancy, and miscarriage rates (P &amp;gt; 0.05). Furthermore, mean weight, sex ratio, and congenital anomaly rates for the 107 and 7 children born in the TV and IV groups, respectively, were not significantly different than those for the 175 children born in the control group. In examining ICM leakage, the mean area before leakage was 3162.6 µm2 and mean area of leaked ICM was 1292.1 µm2 in the IV group, with an average of 40.9% of ICM leaking outside the clear zone. ROC analysis showed that the cutoff for ICM leakage rate for pregnancy was 53.6%, with significantly lower pregnancy rates when the ICM leakage rate was ≥53.6% (18.2% [2/11] vs 65.2% [15/23], p = 0.0255, Fisher’s exact test). Limitations, reasons for caution This study was conducted at a single in vitro fertilization center. Pregnancy, miscarriage, and fetal anomaly rates at birth related to embryo transplantation are based on ongoing pregnancy dates, and complete live birth data for all pregnancies are not yet available. Wider implications of the findings No differences in pregnancy outcomes or fetal anomalies were found among groups. However, pregnancy rates decreased when ICM leakage rates were over 53.6%. Blastocysts with IV may successfully establish a pregnancy, but considering the leaked ICM proportion is crucial. If considered for transplantation, obtaining sufficient informed consent is essential. Trial registration number not applicable

P-132 Outcomes of blastocyst transfer derived from oocytes with smooth endoplasmic reticulum clusters (sERC)

Abstract Study question Are blastocysts derived from oocytes with smooth endoplasmic reticulum clusters (sERC+) as suitable for transfer as those from oocytes without such clusters (sERC-)? Summary answer Blastocysts from sERC+ oocytes are considered for embryo transfer; however, it is recommended to prioritize them lower than those from sERC- oocytes. What is known already One of the cytoplasmic abnormalities in human oocytes, sERC, typically manifests during the MII stage oocytes and disappears after fertilization when the female and male pronuclei emerge. Despite this, the mechanism behind sERC development remains unclear. While it is suggested that sERC in oocytes may adversely impact embryo development and implantation, a definitive conclusion on its safety or use has not been reached. Although the 2011 Istanbul consensus discouraged injecting or inseminating sERC+ oocytes, a 2017 expert panel reconsidered this recommendation, advocating for a case-by-case approach. Therefore, there are widespread variations in responses to sERC in clinical practices. Study design, size, duration A retrospective review of intracytoplasmic sperm injection (ICSI) cycles between April 2014 and April 2023 was conducted, exclusively on single frozen blastocyst transfers of two pronuclei (2PN)-derived embryos performed before June 2023. A dataset comprising 95 blastocysts from sERC+ oocytes and 8,698 blastocysts from sERC- oocytes was assembled. To reduce bias between groups, maternal age at retrieval and transfer counts were matched in a 1:1 ratio using propensity score matching, yielding 95 comparable cycle pairs. Participants/materials, setting, methods Among all ICSI cycles, 78 exclusively involved embryos from sERC+ oocytes, 847 included embryos from both sERC+ and sERC- oocytes, and 6,599 had no embryos derived from sERC+ oocytes. Among the 8,698 sERC- blastocysts transferred, 1,083 and 7,615 originated from cycles with and without sERC+ oocytes, respectively. Implantation, miscarriage, and live birth rates were then compared in 95 matched pairs of blastocysts derived from sERC+ and sERC- oocytes. Main results and the role of chance Following propensity score matching adjustments, the mean patient age at retrieval (mean ± SD) for blastocyst transfers derived from sERC+ and sERC- oocytes were 38.6 ± 4.7 years and 38.7 ± 4.8 years, respectively (p = 0.927). The transfer counts were 4.2 ± 3.4 times for sERC+ and 4.1 ± 3.1 times for sERC- blastocyst transfers (p = 0.840). The proportion of high-quality blastocysts was 48.4% for sERC+ transfers and 54.7% in sERC- transfers (p = 0.384). The implantation rates were 24.2% for sERC+ and 32.6% for sERC- transfers (p = 0.198), miscarriage rates were 43.5% vs. 35.5% (p = 0.552), and live birth rates were 13.7% vs. 21.1% (p = 0.172), respectively, with no statistically significant differences. Thirteen live births from sERC+ blastocyst transfers were recorded, and no congenital abnormalities were observed. Limitations, reasons for caution This study exclusively centered on oocytes subjected to ICSI, and the inclusion criteria were restricted to embryos derived from sERC+ oocytes in accordance with clinic policy limitations. Preimplantation genetic testing was not performed on the majority of the transferred embryos. Wider implications of the findings No congenital abnormalities were observed in live births resulting from sERC+ derived blastocyst transfers. However, the limited number of embryo transfers involving sERC+ oocytes poses a constraint in drawing a definitive conclusion regarding the safety of embryos from sERC+ oocytes, and further data is required. Trial registration number non-clinical trials

P-240 Is the intelligent Data Analysis Score (iDAScore) a reliable tool to predict pregnancy? Our center’s experience

Abstract Study question Is the intelligent Data Analysis Score (iDAScore) reliable in predicting a positive pregnancy test, clinical pregnancy and miscarriage rate after single vitrified-warmed blastocyst transfer (SVBT)? Summary answer There is a significant increase in positive pregnancy test and clinical pregnancy rates as iDAScore increases. The miscarriage rate is lower with increased iDAScore. What is known already With the improvement of assisted reproductive technology (ART), elective single embryo transfer has become a standard. Optimizing embryo selection is a major challenge to increase reproductive outcomes. The Gardner embryo grading system is widely adopted for the evaluation of blastocyst quality, but this tool is subject to inter- and intra-variability. In recent years, artificial intelligence has found diverse applications in healthcare. Based on time-laps sequences of &amp;gt; 180’000 developing embryos, iDAScore is a new deep-learning model for objective and standardized blastocyst scoring. However, its reliability in predicting pregnancy and miscarriage rates remains unknown. Study design, size, duration This monocentric retrospective pilot study was conducted from May 2023 to December 2023. A total of 206 homologous SVBT cycles from 206 patients were analyzed (one patient, one cycle). Exclusion criteria included: cycles involving preimplantation genetic testing, multiple and/or fresh blastocyst transfer, and blastocysts obtained after testicular sperm extraction. All vitrified-warmed blastocysts were scored using iDAScore version 1.0 model, ranging from 1 – 9.9. Participants/materials, setting, methods Scores were stratified into 3 groups: high-score (9.9 – 7.7), medium-score (7.6 – 5.5) and low-score (5.4 – 3.1). For each group, positive pregnancy test, clinical pregnancy and miscarriage rates were analyzed. SVBT cycles were then stratified into four maternal age groups (&amp;lt; 35, 35-37, 38-40, &amp;gt;41 years) and the same outcomes were analyzed. χ2 was used for statistics analysis. Main results and the role of chance Mean maternal age was 36.8 ± 4.9. Among the 206 vitrified-warmed blastocysts, 122 were scored as high-score, 57 as medium-score and 27 as low-score. Positive pregnancy test rate was significantly higher with increased iDAScore with 58% in the high-score group, 36.8% in the medium-score group and 17% in the low-score group (p &amp;lt; 0.0001). Clinical pregnancy rate, defined as the visualization of a fetal heartbeat at ultrasound scan, was also significantly higher with increased iDAScore, with 51.6% in the high-score group, 31.6% in the medium-score group and 17% in the low-score group (p &amp;lt; 0.0001). The miscarriage rate was lower with increased iDAScore, with 8.1% in the high-score group, 16.6% in the medium-score group and 50% in the low-score group, but this difference was not statistically significative (p 0.032). When adjusted to age group however, the miscarriage rate was found to be significantly lower in the high-score group when compared to the medium-score group (p &amp;lt; 0.0001); statistical analysis was not achieved in the low-score group due to the small sample size. Limitations, reasons for caution The major limitation of our study is its small sample size. Data collection is ongoing, to increase the study power. Additionally, many other factors, such as genetic, hormonal, metabolic and/or immunological, may play a role in achieving pregnancy. Wider implications of the findings Our results indicate that iDAScore may be a strong predictor of pregnancy and could be used as a complementary tool to the Gardner embryo grading system in the decision-making process of which blastocyst to transfer. Trial registration number N/A

P-403 Does a thick endometrium really matter? It’s impact on FET cycles results

Abstract Study question Does a thick endometrium negatively affect the results of FET cycles after PGT? Summary answer Endometrial thickness above 10mm did not affect pregnancy rates, and live birth rates were even higher in the group with thick endometrium. What is known already The success of an assisted reproduction technique leads on two main points: getting a high-quality embryo and a functional endometrium. The results of the relationship between a thick endometrium and its influence on the pregnancy rates are contradictory till the date, mainly due to the relatively reduced sample sizes and the presence of confoundings. In the same way, they are scarce the papers that analyze the results of FET under hormone replacement therapy in cycles with euploid blastocysts. These cycles could be considered the gold standard to establish the influence of thick endometria in the implantation rate. Study design, size, duration Retrospective study of FET cycles under hormone replacement therapy with transfer of an euploid blastocyst after PGT. Multicentric analyze of cycles performed between 2015 and 2021 in our Spanish IVIRMA clinics. Participants/materials, setting, methods We analyzed 3158 cycles of FET under hormone replacement therapy with transfer of an euploid blastocyst. Hormone therapy consisted in estrogens (etinil estradiol orally or in patches), plus progesterone (400 mg/ 12 hours, vaginally). Two groups were established: an “optimal” endometrial thickness (7 - 10mm) (80.81%), and those with a higher one (19.19%), the day that the transfer was planned. The objective was to analyze the implantation, miscarriage and live birth rates. Main results and the role of chance Both groups were comparable in terms of age, origin an age of the oocytes, origin of the sperm, and serum estradiol levels the day that the embryo transfer was programmed. There were differences in the BMI of the patients (23.00 Vs 23.51, p = 0.004) and the day of the cycle that the embryo transfer was planned (11.8 Vs 11.78, p &amp;lt; 0.001). There were no differences regarding hormonal treatment protocol or dose, nor regarding cycle monitoring. There were not significant differences in the implantation rate between the group with an endometrial thickness between 7 and 10mm (62.84%; CI 95% 60.90 – 64.78) and the one with a thicker endometrium (66.08%; CI 95% 62.19-69.98; p = 0.143). Neither in the miscarriage rate (15.76%, CI 95% 14.36-17.24; Vs 14.40%, CI 95% 11.70-17.46; p = 0.444). Statistically significant differences were found in the live birth rate, which was of 47.74% in the group of endometrial thickness between 7 and 10mm (CI 95% 45.75-49.73), and 53.20% in the group with a thicker endometrium (CI 95% 49.09-57.27, p = 0.019) Taking these results into account, we could conclude that a thick endometrium does not negatively affect the results of FET cycles. Limitations, reasons for caution The nature of our study was retrospective not randomized. It was performed with euploid embryos under hormone replacement treatment. Thus, results may not be applicable in other settings. The measure of the endometrial thickness is very variable between professionals and there can be more factors involved in the functionality. Wider implications of the findings Embryo transfer should not be canceled in cases of endometrial thickness &amp;gt; 10 mm. More studies are needed to ascertain if it would be beneficial to achieve systematically an endometrial thickness &amp;gt; 10 mm Trial registration number Not applicable

P-435 Superiority of modified natural cycle vs hormonal replacement therapy in non-menopausal egg recipients of advanced maternal age: clinical outcomes from 1273 single blastocyst transfer cycles

Abstract Study question Is the modified natural cycle (mNC) better than hormonal replacement therapy (HRT) for endometrial preparation in non-menopausal egg recipients of advanced maternal age? Summary answer In women above 40 years, mNC shows better reproductive and obstetrical outcomes compared to hormonal replacement therapy, especially in the subgroup 45-50 years old. What is known already There is extensive evidence showing the superiority of mNC over HRT in terms of live birth rates, miscarriages, and even obstetric complications. Apparently, the presence of the corpus luteum plays a major role in endometrial receptivity and embryo implantation, probably allowing for better placentation. Nevertheless, there is a general belief that the ovulatory cycle of older women is not the best choice for endometrial preparation, although paradoxically they are the group of patients who could benefit most from the reduction of obstetric complications. An increase in cancellation rates for mNC is claimed, without consistent data available. Study design, size, duration Retrospective single-centre comparative clinical study, including 1273 endometrial preparation cycles for frozen single-blastocyst transfer between January 2020 and December 2022: 892 (70,2%) on HRT protocol and 381 (29,8%) on mNC protocol. The two groups were homogeneous for donor’s age (25,7 years HRT vs 25,3 years mNC), recipient’s age (42,2 years HRT vs 42,1 years mNC), severe male factor (6% HRT vs 5% mNC), and the need for a sperm donor (28% HRT vs 26% mNC). Participants/materials, setting, methods Among 1273 started non-menopausal recipient’s cycles, we compared cancellation rates between HRT and mNC due to either medical reasons (inadequate endometrium, bleeding, premature ovulation) or other issues (no embryo survival, COVID-19, etc). We studied the outcomes of the 1096 elective frozen single-blastocyst transfers performed, comparing HRT and mNC cycles for: pregnancy, clinical pregnancy, miscarriage, live birth and &amp;lt;35weeks preterm birth rates. We stratified the results by age and used Chi-square test to compare groups (p &amp;lt; 0,05). Main results and the role of chance The overall cancellation rate was 13.9%. No significant differences in cancellation for medical reasons were found between HRT (7%) and mNC (6.8%), p = 0.93. When we analyse results stratified by age, patients aged 39 or less (270 cycles: HRT 75.9%, mNC 24.1%) showed no statistically significant differences in pregnancy (58% vs 64.6%, p = 0.35), clinical pregnancy (50.7% vs 56.9%, p = 0.34), miscarriage (18.3% vs 18.9%, p = 0.93), and live birth rates (41.5% vs 46.2%, p = 0.5). In the 40-44 age group (494 cycles: HRT 64.2%, mNC 35.8%), no statistically significant differences were found between HRT and mNC in pregnancy (58.2% vs 61.5%, p = 0.47), clinical pregnancy (50.8% vs 51.1%, p = 0.96), and live birth rates (40.4% vs 45.8%, p = 0.25). The HRT group had a significantly higher miscarriage rate (21%) compared to mNC (10%), p = 0.03. For patients aged 45-50 years (332 cycles: HRT 72%, mNC 28%), no statistically significant differences were observed in pregnancy (56.5% vs 62.4%, p = 0.33) and miscarriage rates (24.3% vs 15.1%, p = 0.18). Clinical pregnancy (44.8% Vs 57%, p = 0.04) and live birth rates (33.9% vs 48.4%, p = 0.01) were significantly higher in the mNC group compared to HRT. No significant differences were found between HRT and mNC in preterm birth rates &amp;lt;35 weeks (3.6% vs 4.6%, p = 0.75). Limitations, reasons for caution This study is a single-centre retrospective comparative trial. Our homogeneity study included several confounding variables, however other bias such as severe uterine factor, embryo quality or repeated implantation failure cases were not taken into account. Wider implications of the findings Modified natural cycle should be encouraged as the first option for endometrial preparation in non-menopausal egg recipients of advanced maternal age, having shown superiority over hormonal replacement therapy in patients aged 45-50 years. Moreover, modified natural cycles are more patient friendly and cost-effective, with no increase in the cancellation rates. Trial registration number not applicable

P-184 Clinical effectiveness of the embryo scoring system based on a morpho-kinetic evaluation, the Eeva™ Test, on results of single blastocyst transfer

Abstract Study question Can the implementation of morpho-kinetic assessment optimize blastocyst selection for successful implantation, thereby minimizing the number of transfer cycles required to achieve pregnancy? Summary answer There was no significant difference in the number of transfer cycles required to achieve clinical pregnancy between evaluation methods using Eeva™ Test and conventional method. What is known already Numerous investigations have recently been conducted on the efficacy of morpho-kinetic assessment of embryos; nevertheless, these studies have solely substantiated pregnancy prediction. As there are limited reports employing it for embryo selection, clinical evidence demonstrating its utility in enhancing live birth rates and minimizing the number of embryo transfers required for pregnancy remains elusive. The timing of embryonic division and direct cleavage serve as prevalent prognostic markers for predicting blastocyst formation. The present investigative study employs the Eeva™ which appropriately incorporates these indicators. Study design, size, duration Prospective single-center study. This study included couples who underwent their first oocyte retrievals and subsequently underwent a frozen-thawed single blastocyst transfer from March 2019 to December 2020. The participants were divided into two groups: Group G, in which the embryos were cultured in a time-lapse incubator (Geri®+), and evaluated by Gardner score and Eeva™ Test, and Group D, in which the embryos were cultured in a conventional dry incubator and evaluated morphologically by Gardner score. Participants/materials, setting, methods The study enrolled a total of 217 participants. We conducted a comparative analysis of clinical pregnancy, miscarriage, and live birth rates between the two groups. Additionally, in 168 clinically pregnant cases, the proportion of the cases who achieved clinical pregnancy following the first embryo transfer and the number of transfer cycles required for clinical pregnancy between the two groups were compared. Main results and the role of chance There were no significant differences in clinical pregnancy rates (83/187, 44.4% vs. 98/203, 48.3%), miscarriage rates (12/83, 14.5% vs. 21/98, 21.4%), and live birth rates (69/187, 36.9% vs. 76/203, 37.4%) between group G and D. Among the cases of clinical pregnancy, no significant differences were observed in the proportion of cases attaining clinical pregnancy following the initial embryo transfer (55/77, 71.4% vs. 65/91, 71.4%) and the number of cycles required to achieve clinical pregnancy (1.42 ± 0.78 vs. 1.44 ± 0.88) between group G and D. Limitations, reasons for caution While the Eeva™ considers the timing of embryonic division and direct cleavage, other indicators are not taken into account. Consequently, it is necessary to authenticate clinical validity of morpho-kinetic assessment for blastocyst selection also via a methodology that incorporates those elements. Wider implications of the findings No significant differences were observed between Eeva™ and the conventional method. The clinical effectiveness of the blastocyst selection based on Eeva™ scores could not be substantiated. Hence, evaluating solely blastocyst morphology is considered satisfactory at present, and morpho-kinetic assessment of cleavage-stage embryos is not necessary for blastocyst selection. Trial registration number not applicable