Fresh Embryo Transfer Research Articles

Effect of sequential cleavage and blastocyst embryo transfer compared to single cleavage stage embryo transfer on assisted reproductive technology outcome: An RCT.

Assisted reproductive technology (ART), offers hope for many infertile couples by increasing the chance of successful pregnancy. The success of in vitro fertilization depends on various factors, in which embryo transfer (ET) is one of the critical steps influencing in vitro fertilization success rates. Extended embryo culture and blastocyst-stage ET have been considered in ART due to their potential benefits including improved implantation rates. This study aimed to compare the outcomes of sequential ET vs single cleavage-stage ET in women undergoing a fresh ET cycle with a limited number of embryos. This randomized clinical trial was conducted on 140 women undergoing infertility treatments and candidates for fresh ET at the Research and Clinical Center for Infertility, Yazd, Iran from August 2023 to January 2024. Women with a number of embryos from 2-5 ( 2 and 5 available embryos) were randomly divided into 2 groups: One group underwent sequential ET (one cleavage-stage ET followed by one blastocyst ET) and the other group underwent single-step 2 cleavage-stage ET. The primary outcome was clinical pregnancy, and the secondary outcome included chemical pregnancy and early abortion rates. Our findings showed significantly higher rates of clinical (33.5% vs 13.6%, p = 0.003) and chemical (41.3% vs 18.2%, p = 0.004) pregnancies in the sequential ET group compared to the single-step cleavage ET group. The early abortion rate was higher in single-step cleavage ET (13% vs 44.4%, p = 0.053). Sequential fresh ET is a useful choice in women who have a limited number of embryos and can improve ART outcomes.

The good, the bad and the ugly of luteal phase stimulations

An early follicular phase start of ovarian stimulation in assisted reproductive technology (ART) is only required if a fresh embryo transfer is planned. A shift from fresh to frozen embryo transfers has recently characterized ART treatments and, combined with the trend towards treatment individualization and simplification, facilitated random-start stimulation. Luteal phase stimulation, started between ovulation and the next menses, has gained momentum and the good, the bad and the ugly sides have become obvious with the increasing number performed. Unprotected intercourse during the follicular phase or around ovulation can result in an unknown and undetectable conception at the time of starting stimulation. Aside from the theoretical implications for embryo development from exposure to stimulation medication, embryo-derived human chorionic gonadotrophin may cause ovarian hyperstimulation syndrome. The duration of stimulation and consumption of gonadotrophin appear to be longer and higher than in the early follicular phase start approach, although the number of retrieved/mature oocytes is comparable or, in some instances, higher. On the other hand, elevated progesterone concentrations during the luteal phase may prevent premature ovulation and, in theory, might replace pituitary suppression using gonadotrophin-releasing hormone antagonists or exogeneous progestins. Furthermore, the flexibility in stimulation timing will meet the needs of patients with time constraints.

Using progesterone to follicular index ratio is better correlated with intracytoplasmic sperm injection outcome than using serum progesterone level alone.

to investigate the possibility of using the ratio of serum progesterone level to the number of follicles, according to ovarian response in the day of human chorionic gonadotrophin trigger, as a predictor of cycle outcome. A prospective intervensional study was conducted at Kamal Al-Samarai Hospital for Infertility Treatment and IVF during the period from December 2020 to September 2021. Ninety infertile women underwent intracytoplasmic sperm injection (ICSI) cycles using antagonist protocol. Moreover, once the patient reached triggering criteria, meticulous recording of follicular index together with serum estrogen level and serum progesterone level are measured. Fresh embryo transfer of cleavage stage embryo is done once serum progesterone level was less than 1.5 ng/mL. A follow-up to confirm pregnancy rate and cycle outcome was done. The study showed a positive pregnancy rate of 28.9%. The relationship between progesterone follicular index (Prog/FI) ratio and (ICSI) outcome was highly significant with a p value of 0.001. Additionally, an inverse relationship, as the ratio was lower the pregnancy rate was improved, was documented. The receiver operating characteristic (ROC) curve for progesterone follicular index ratio was 0.711 with a cut off value of 0.0354 ng/mL in addition to a sensitivity of 65.6 and a specificity of 65.4. The serum progesterone level is an independent factor for the prediction of intracytoplasmic sperm injection (ICSI) outcome, whereas the progesterone follicular index ratio can be used as a potential marker for predicting ICSI outcome in fresh embryo transfer.

Comparisons of cumulative live birth rates after embryo transfers at day 2/3 versus day 5/6: a French national study

Research questionAre there significant differences between cumulative live birth rates (CLBR) after short or extended embryo culture when comparisons are performed per cycle? DesignThis French national study included all IVF cycles performed from January 2016 to December 2019 with at least one cleaved embryo at day 2. The day 2/3 and day 5/6 groups were identified using the National Biomedicine Agency register. Only attempts involving the vitrification method were included. CLBR was assessed with 1 and 2 years of follow-up using a logistic regression model. The evolution of CLBR per cycle was compared over 1 year of follow-up. ResultsIn total, 133,250 cycles met the inclusion criteria (70,528 and 62,722 in the day 2/3 and day 5/6 groups). In multivariate analysis including several patient and cycle characteristics, the CLBR per cycle was significantly lower in the day 5/6 compared with the day 2/3 group. A significantly higher rate of fresh embryo transfer cancellation was observed in the day 5/6 compared with the day 2/3 group. The evolution of the CLBR was significantly different in favour of the day 2/3 group in cases with three or fewer day 2 embryos, whatever the patient's age, in their two first attempts as well as in their third or further attempts. ConclusionsOverall, the nationwide results per cycle suggest that extended embryo culture until the blastocyst stage, even when used in combination with vitrification, could not improve live birth rates. Moreover, where three or fewer day 2 embryos are obtained, it might be preferable to use the short embryo culture strategy.

Establishment of a predictive nomogram for clinical pregnancy rate in patients with endometriosis undergoing fresh embryo transfer

To establish a nomogram model for predicting clinical pregnancy rate in patients with endometriosis undergoing fresh embryo transfer. We retrospectively collected the data of 464 endometriosis patients undergoing fresh embryo transfer, who were randomly divided into a training dataset (60%) and a testing dataset (40%). Using univariate analysis, multiple logistic regression analysis, and LASSO regression analysis, we identified the factors associated with the fresh transplantation pregnancy rate in these patients and developed a nomogram model for predicting the clinical pregnancy rate following fresh embryo transfer. We employed an integrated learning approach that combined GBM, XGBOOST, and MLP algorithms for optimization of the model performance through parameter adjustments. The clinical pregnancy rate following fresh embryo transfer was significantly influenced by female age, Gn initiation dose, number of assisted reproduction cycles, and number of embryos transferred. The variables included in the LASSO model selection included female age, FSH levels, duration and initial dose of Gn usage, number of assisted reproduction cycles, retrieved oocytes, embryos transferred, endometrial thickness on HCG day, and progesterone level on HCG day. The nomogram demonstrated an accuracy of 0.642 (95% CI: 0.605-0.679) in the training dataset and 0.652 (95% CI: 0.600-0.704) in the validation dataset. The predictive ability of the model was further improved using ensemble learning methods and achieved predicative accuracies of 0.725 (95% CI: 0.680-0.770) in the training dataset and 0.718 (95% CI: 0.675-0.761) in the validation dataset. The established prediction model in this study can help in prediction of clinical pregnancy rates following fresh embryo transfer in patients with endometriosis.

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...

Undetected, natural conception pregnancies in luteal phase stimulations-case series and review of literature.

What is the risk of an undetected natural conception pregnancy during luteal phase ovarian stimulation, and how does it impact the pregnancy's course? The risk for an undetected, natural conception pregnancy in luteal phase ovarian stimulation is low and it appears that ovarian stimulation is unlikely to harm the pregnancy. Random start ovarian stimulation appears to be similarly effective as early follicular stimulation start; and it allows ovarian stimulation to be started independent of the cycle day and throughout the cycle, in accordance with the patients' and clinics' schedule as long as there is no intention of a fresh embryo transfer in the same cycle. Starting ovarian stimulation in the luteal phase bears the possibility of an-at the timepoint of stimulation start-undetected, natural conception pregnancy that has already occurred. There is scarce data on the incidence of this event as well as on the possible implications of ovarian stimulation on the course of an existing pregnancy. This retrospective observational study, performed between June 2017 and January 2024, analyzed luteal phase stimulations, in which a natural conception pregnancy was detected during the ovarian stimulation treatment for IVF/ICSI. Luteal phase stimulation was defined as ovarian stimulation started after ovulation and before the next expected menstrual bleeding, with a serum progesterone (P4) level of >1.5 ng/ml on the day of stimulation start or 1 day before. Women who underwent a luteal phase ovarian stimulation in a tertiary referral ART center. A total of 488 luteal phase stimulation cycles were included in the analysis. Luteal phase stimulation was only started after a negative serum hCG measurement on the day or 1 day before commencement of ovarian stimulation. Ten patients (2.1%) had an undetected natural conception pregnancy at the time of luteal phase stimulation start. Eight of these patients underwent an ovarian stimulation in a GnRH-antagonist protocol and two in a progestin-primed stimulation protocol (PPOS). Recombinant FSH was used as stimulation medication for all patients, the patients with a PPOS protocol received additional recombinant LH. One pregnancy (0.2%) was detected after the oocyte retrieval, the other nine pregnancies were detected either due to persistent high serum progesterone levels or due to an increasing progesterone level after an initial decrease before oocyte retrieval. In the cycles with an undetected natural conception pregnancy, the median number of stimulation days was 8 days (range: 6-11 days) and median serum hCG at detection of pregnancy was 59 IU hCG (range: 14.91-183.1). From 10 patients with a pregnancy, three patients delivered a healthy baby, two patients had ongoing pregnancies at the time of summarizing the data, three patients had biochemical pregnancies (patient age: 30, 39, and 42 years), one patient had an ectopic pregnancy which required a salpingectomy, and one patient (age: 34 years) had an early pregnancy loss. The retrospective study design and the small sample size can limit the accuracy of the estimates. Overall, there is a small risk of undetected natural conception pregnancies when luteal phase stimulation is undertaken. It appears that there are no adverse effects through either direct effect on the embryo or indirectly through a detrimental effect on the corpus luteum function on the pregnancy in our cohort. This study did not receive funding. The authors declare that there is no conflict of interest. N/A.

Live Birth after Cleavage-Stage versus Blastocyst-Stage Embryo Transfer in Assisted Reproductive Technology: A Randomised Controlled Study.

Blastocyst stage transfer appears to improve pregnancy outcomes. The aim of this study is to evaluate the pregnancy results between fresh cycle blastocyst stage embryo transfer and cleavage stage embryo transfer in patients who undergo intracytoplasmic sperm injection (ICSI). This randomised clinical trial study was conducted at the Infertility Research Centre of Milad Hospital in Mashhad, Iran from 2018 to 2020 on 240 infertile women who presented for their first ICSI procedure. These patients were assigned to receive either cleavage embryo transfer (n=112) or blastocyst stage transfer (n=107). Pregnancy outcomes were measured in both groups. There were no differences regarding age, body mass index (BMI), serum follicle-stimulating hormone (FSH), duration of infertility, and aetiology of infertility between the groups (P>0.05). There were more follicles, total oocytes, and metaphase II (M2) oocytes in the blastocyst stage group. Considerably more cleavage stage embryos were transferred compared to the number of transferred blastocysts (P=0.001). The blastocyst group had more vitrified embryos than the cleavage group (P=0.000). The rates of implantation (P=0.332), chemical pregnancy (P=0.165), clinical pregnancy (P=0.694), and live births (P=0.727) were higher in the blastocyst group, but they were not significantly different. The rate of abortion was also not significantly higher in the blastocyst group (P=0.296). Blastocysts transferred in the fresh cycle of an ICSI procedure may be more advantageous compared to cleavage stage embryo transfer (registration number: IRCT20181030041503N1).

Safety of embryo cryopreservation: insights from mid-term placental transcriptional changes

BackgroundIn recent years, with benefits from the continuous improvement of clinical technology and the advantage of fertility preservation, the application of embryo cryopreservation has been growing rapidly worldwide. However, amidst this growth, concerns about its safety persist. Numerous studies have highlighted the elevated risk of perinatal complications linked to frozen embryo transfer (FET), such as large for gestational age (LGA) and hypertensive disorders during pregnancy. Thus, it is imperative to explore the potential risk of embryo cryopreservation and its related mechanisms.MethodsGiven the strict ethical constraints on clinical samples, we employed mouse models in this study. Three experimental groups were established: the naturally conceived (NC) group, the fresh embryo transfer (Fresh-ET) group, and the FET group. Blastocyst formation rates and implantation rates were calculated post-embryo cryopreservation. The impact of FET on fetal growth was evaluated upon fetal and placental weight. Placental RNA-seq was conducted, encompassing comprehensive analyses of various comparisons (Fresh-ET vs. NC, FET vs. NC, and FET vs. Fresh-ET).ResultsReduced rates of blastocyst formation and implantation were observed post-embryo cryopreservation. Fresh-ET resulted in a significant decrease in fetal weight compared to NC group, whereas FET reversed this decline. RNA-seq analysis indicated that the majority of the expression changes in FET were inherited from Fresh-ET, and alterations solely attributed to embryo cryopreservation were moderate. Unexpectedly, certain genes that showed alterations in Fresh-ET tended to be restored in FET. Further analysis suggested that this regression may underlie the improvement of fetal growth restriction in FET. The expression of imprinted genes was disrupted in both FET and Fresh-ET groups.ConclusionBased on our experimental data on mouse models, the impact of embryo cryopreservation is less pronounced than other in vitro manipulations in Fresh-ET. However, the impairment of the embryonic developmental potential and the gene alterations in placenta still suggested it to be a risky operation.

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.

Trophectoderm grade as a predictor of beta human-chorionic gonadotropin rise in early pregnancy.

To evaluate the association, if any, between the grade of the trophectoderm (TE) and the rate at which β-human-chorionic gonadotropin (β-HCG) rises in early pregnancy. This is a retrospective cohort study including 1116 singleton clinical pregnancies resulting from in vitro fertilization with single day 5 blastocyst transfer at an academic fertility center. TE quality was assessed by trained embryologists employing standard criteria. Three groups were formed based on the TE grade: grade A (n = 358), grade B (n = 628), and grade C (n = 130). Main outcome measure was the rise (%) in serum levels of β-HCG (days 12 to 14 post embryo transfer), using the following formula [(β-HCG D14 - β-HCG D12) * 100/β-HCG D12]. Fresh embryo transfers accounted for 64.1% of the population. Overall, in adjusted models there were no significant differences in the β-HCG% rise when comparing the TE grade C group to TE grade A [adjβ (95%CI): 10.09 (- 0.05, 20.22)] or when comparing TE grade Β group to TE grade A [4.46 (- 2.97, 11.88)]. When the analysis was restricted to fresh embryo transfers, significant differences were observed in the % rise of β-HCG when comparing the TE grade C group to TE grade A [adjβ (95%CI): 21.71 (5.67, 37.74)], but not when comparing the TE grade B group to TE grade A [2.68 (- 5.59, 10.95)]. In frozen transfers, there were no significant differences. TE grade appears to impact early pregnancy serum β-HCG levels in the setting of a fresh day 5 embryo transfer, even after adjusting for potential confounders.

Antimüllerian Hormone Association with Polycystic Ovary Syndrome and Pregnancy Outcomes of in Vitro Fertilization Cycles with Fresh Embryo Transfer

Antimüllerian Hormone Association with Polycystic Ovary Syndrome and Pregnancy Outcomes of in Vitro Fertilization Cycles with Fresh Embryo Transfer

P-695 Optimizing oocyte donor stimulation: A revelation from 2,666 cases emphasizing the sole efficacy of exogenous FSH

Abstract Study question Does the administration of human menopausal gonadotrophin in controlled ovarian stimulation improve clinical outcomes in the oocyte donation program? Summary answer The addition of hMG (human menopausal gonadotropin) reduces the number of retrieved oocytes without improving embryo development or clinical outcomes in oocyte donation program. What is known already In controlled ovarian stimulation for assisted reproduction treatments, follicle stimulating hormone(FSH) is essential, but the importance of LH supplementation from menopausal origin is controversial. It is a common practice to use hMG to provide the LH effect. The standard preparation contains FSH and LH effects in a 1:1 ratio.The FSH component would recruit ovarian follicles and stimulate their growth, while the LH component would facilitate their maturation. Our aim was to compare the outcomes of intracytoplasmic sperm injection (ICSI) treatments using a gonadotropin-releasing hormone GnRH) antagonist protocol with recombinant FSH(FSHr) alone and supplemented with hMG in the oocyte donation program. Study design, size, duration This is a retrospective cohort study of 2,666 patients enrolled in the oocyte donation program at a single center over four consecutive years. Donor stimulation commenced with daily FSHr injections. The FSHr group (n = 2,078) continued FSHr, while the FSHr+hMG group (n = 588) received hMG. Participants/materials, setting, methods Donors received GnRH agonist via i.m. injection until a mean diameter >18 mm in at least eight follicles. Transvaginal oocyte retrieval was scheduled 36h later, followed by ICSI for all retrieved oocytes. Embryos were cultured in time-lapse systems and evaluated using an artificial intelligence-based model (iDAScore v2). Recipients underwent hormone replacement therapy for endometrial preparation. Our comparative study examined oocytes retrieved, embryo score, implantation, and live birth outcomes in fresh and frozen embryo transfers (ETs). Main results and the role of chance The number of retrieved oocytes was higher in the FSHr group than in the FSHr+hMG group: 24.9±10.6 vs. 18.2±8.8 (p < 0.001). In addition, embryos from the FSHr+hMG group exhibited slower early development, with significantly lower division times to two, three, four and five cells in the FSHr group (p < 0.005). However, late parameters of embryo development showed no differences. Automatic scoring by the deep learning algorithm was identical for blastocysts in the FSHr (4.8±2.8) and FSHr+hMG groups (4.8±2.8); p = 1. Implantation rates showed no significant differences for fresh ET (FSHr: 58.6% vs. FSHr+hMG: 61.9%; n = 2,073; p = 1) or frozen ET (FSHr: 49.3% vs. FSHr+hMG: 46%; n = 2,687; p = 1). Similarly, there were no differences in live birth rates for fresh ET (FSHr: 45.6% vs. FSHr+hMG: 50.3%; n = 1,993; p = 1) or frozen ET (FSHr: 31.8% vs. FSHr+hMG: 33.8%; n = 2,508; p = 1). Limitations, reasons for caution The retrospective and single-center nature of the study would be its main limitations. It is essential to emphasize that these results are only applicable within the oocyte donation program. Wider implications of the findings Based on our findings, the use of exogenous FSHr alone is likely adequate in the GnRH antagonist protocol for optimal ovarian stimulation of donors, leading to the production of high-quality embryos and successful clinical outcomes. Trial registration number Not Applicable

O-093 Infant mortality after assisted reproductive technology – a Nordic collaborative study on 7,947,575 liveborn children

Abstract Study question Is infant mortality, i.e., mortality up to one year of age, higher after assisted reproductive technology (ART) than after natural conception (NC)? Summary answer Infant mortality was increased in ART-singletons vs NC-singletons, with similar increased mortality across ART fertilization methods. Infant mortality was not increased in ART-twins vs NC-twins. What is known already Children born after ART have an increased risk of poor perinatal outcomes such as preterm birth and low birth weight, mainly due to the higher twin birth rates in the ART population. ART singletons also carry an increased risk of poor perinatal outcomes as compared to their NC counterparts. Studies on consequences of being born after ART are mostly sparse and inconclusive which also applies to studies on infant mortality. Study design, size, duration A Nordic registry-based study including all children born alive in Denmark (1994–2014), Finland (1990–2014), Norway (1984–2015) and Sweden (1985–2015) resulting in a cohort of 171,836 ART-children and 7,775,739 NC-children. Among ART-children 127,248 (74%) were singletons and 42,569 (25%) twins, and among NC-children 7,576,396 (97%) were singletons and 194,775 (3%) twins. Multiples with >2 children were excluded (<0.1%). All singletons and twins were followed until death, emigration or one year of age. Participants/materials, setting, methods Data originated from national ART-, birth-, and causes of death registers. Infant mortality was compared for ART vs NC singletons and ART vs NC twins in separate analyses using Cox proportional hazards model yielding hazard ratios (HRs) with 95% confidence intervals (95% CIs). Infant mortality in singletons and twins was compared for IVF, ICSI, fresh and frozen embryo transfer vs NC counterparts. Cause-specific death analysis accounted for other causes of death as a competing risk. Main results and the role of chance Overall, 515 (4‰) ART- and 26,076 (3‰) NC-singletons and 615 (14‰) ART- and 3317 (17‰) NC-twins died during infancy. Median age at death was 3 (IQR 0–195) and 10 days (IQR 0–245) for ART- and NC-singletons, respectively, and 1 (IQR 0–151) and 2 days (IQR 0–161) for ART- and NC-twins, respectively. After adjusting for country, parity, maternal age, and birth year, the adjusted HR (aHR) for infant mortality was 1.75 (95% CI 1.60–1.91) for ART-singletons vs NC-singletons, and 0.94 (95% CI 0.86–1.03) for ART-twins vs NC-twins. A higher mortality was found consistently among ART-singletons born after IVF, ICSI, fresh embryo transfer and frozen embryo transfer vs NC-singletons. Infant mortality was consistently similar between ART-twins and NC-twins across treatment methods. Leading causes of death were conditions originating in the perinatal period (23% and 47% of deaths among singletons and twins) with aHR 1.87 (95% CI 1.65–2.12) for ART-singletons vs NC-singletons, and aHR 0.97 (95% CI 0.86–1.10) for ART-twins vs NC-twins, and congenital malformations (19% and 11% of deaths among singletons and twins) with aHR 1.31 (95% CI 1.09–1.58) for singletons and aHR 1.37 (95% CI 1.08–1.74) for ART-twins vs NC-twins. Limitations, reasons for caution Observational studies are prone to confounding. Despite adjustment for some major confounders, residual confounding from underlying parental conditions cannot be excluded. Causes of death may be more complex than the causes registered. Further, 44% of deaths among NC and 12% of deaths in ART were without an assigned cause. Wider implications of the findings Findings that infant mortality is increased among ART- vs NC-singletons corresponds with previous findings of poorer perinatal outcomes in this group. Risks were similar across ART fertilization methods and cryopreservation status. Trial registration number Not applicable

P-753 Obstetric and neonatal risks in 7,378 singletons following fresh and frozen-thawed embryo transfers in Japan: An analysis utilizing doubly robust estimation

Abstract Study question How do obstetric and neonatal risks differ between frozen-thawed embryo transfer (FET) and fresh embryo transfer (FreshET), as well as other non-assisted-reproductive-technology (non-ART) infertility treatments? Summary answer FET demonstrated a significantly higher incidence of obstetric complications, with a discernable but not statistically significant trend toward increased neonatal anomalies. What is known already Several studies indicate that FET is associated with an increased incidence of obstetric complications, encompassing gestational hypertension, placenta accreta, and gestational diabetes. Additionally, reports suggest that ART may elevate the risk of neonatal anomalies, although discerning whether this risk is more prevalent in FET or FreshET remains uncertain. Study design, size, duration This single-center, retrospective cohort analysis was conducted, encompassing 7,378 singletons delivered between January 2013 and December 2022 following fertility treatment within our institution. Within this cohort, cases conceived through controlled ovarian stimulation, timed intercourse, intrauterine insemination, or routine infertility checkups were categorized as the non-ART group. We compared the obstetric complications and neonatal outcomes between the FET and FreshET groups, using the non-ART group as the control. Participants/materials, setting, methods The evaluated outcomes included placenta accreta, placenta previa, postpartum hemorrhage, gestational hypertension, gestational diabetes, preterm birth, placental abruption, neonatal anomalies, high birth weight (≥4,000 g), and low birth weight (<2,500 g). For the statistical analysis, we employed inverse probability weighted regression adjustment (IPWRA). IPWRA integrates outcome regression with a model for exposure (propensity score), ensuring unbiased estimates even if one of the models is misspecified (a doubly robust property). Main results and the role of chance Among the 7,378 singleton births, 2,643 were in the non-ART group, 4,219 in the FET group, and 516 in the FreshET group. Comparative analysis with the non-ART group revealed that the FET group exhibited a higher risk across various obstetric complications, including placenta accreta (adjusted risk difference [ARD] 3.61%, 95% confidence interval [CI] 2.95 to 4.28), placenta previa (ARD 0.55%, 95% CI 0.14 to 0.96), postpartum hemorrhage (ARD 7.08%, 95% CI 6.03 to 8.13), gestational hypertension (ARD 3.57%, 95% CI 2.47 to 4.68), gestational diabetes (ARD 0.96%, 95% CI 0.17 to 1.75), preterm birth (ARD 2.13%, 95% CI 1.23 to 3.02), and high birth weight (ARD 0.97%, 95% CI 0.42 to 1.52). The analysis of neonatal anomalies initially showed a significant risk difference between the FET and non-ART groups in the crude analysis (crude risk difference 0.74%, 95% CI 0.09 to 1.38), although this significance diminished after adjustment (ARD 0.68%, 95% CI -0.02 to 1.39). The FreshET group did not demonstrate an increased risk of obstetric complications or neonatal anomalies. Limitations, reasons for caution The retrospective design of this study, conducted at a single institution, limits the generalizability of its findings to a broader population. Factors inherent to the specific facility, practices, and patient demographics may introduce variability in outcomes. Moreover, the potential for bias from unmeasured confounders cannot be entirely ruled out. Wider implications of the findings The mitigation of the risk of obstetric complications may be achieved through careful selection for FreshET, as opposed to a predominant inclination towards FET. It is crucial to develop a collaborative framework that enables the seamless exchange of information on maternal and neonatal prognoses between ART and perinatal facilities. Trial registration number not applicable

P-162 Embryo transfer impact: a comprehensive national cohort analysis comparing maternal outcomes across varied embryo stages in fresh and frozen transfers

Abstract Study question What is the ideal choice between fresh and frozen embryos transfer, and should the transfer be done at the cleavage or blastocyst stage? Summary answer This study highlights the clinical pregnancy and live birth superiority of frozen embryo transfer in blastocysts but not in cleavage stage embryos. What is known already Frozen embryo transfer not only improves reproductive outcomes by increasing the chances of live birth and clinical pregnancy but also enhances safety by reducing the risks of OHSS and multiple pregnancies. Due to the consistent findings, there has been a growing discussion in recent years about whether it is advisable to adopt elective frozen embryo transfer as the standard practice. Study design, size, duration In this retrospective cohort study conducted in Taiwan, a comprehensive dataset from the national assisted reproductive technology (ART) database was utilized, covering the period from January 1st, 2013, to December 31st, 2017. The final cohort study encompassed eligible 51762 female participants who had undergone ART and embryo transfer. Pregnancy outcomes and maternal complications during the follow-up were assessed using the population registry dataset from January 1st, 2013, to December 31st, 2018. Participants/materials, setting, methods The study categorizes cases into groups based on whether they underwent fresh or frozen embryo transfers, with additional subgroups based on cleavage stage and blastocyst stage transfers. Exposure variables include clinical pregnancy rate, live birth rate, ovarian hyperstimulation syndrome (OHSS), pregnancy-induced hypertension, gestational diabetes mellitus (DM), placenta previa, placental abruption, and preterm premature rupture of membranes (PPROM). Main results and the role of chance For pregnancy outcomes, frozen blastocyst transfers exhibited higher rates of clinical pregnancy (OR 1.33, 95%CI 1.25-1.42) and live births (OR 1.27, 95%CI 1.19-1.36) when compared to fresh blastocyst transfers. However, frozen cleavage stage transfers had lower rates of clinical pregnancy (OR 0.73, 95%CI 0.69-0.77) and live births (OR 0.79, 95%CI 0.74-0.84) compared to fresh cleavage stage transfers. For maternal complications, frozen embryo transfers were associated with reduced risks of OHSS (OR 0.02, 95%CI 0.02-0.03 for blastocyst and OR 0.05, 95%CI 0.03-0.09 for cleavage stage) compared to fresh embryo transfers, but were linked to a higher risk of pregnancy-induced hypertension (OR 1.43, 95%CI 1.19-1.73 for blastocyst and OR 1.23, 95%CI 1.29-1.82 for cleavage stage). No significant differences were observed in the incidence of gestational DM and PPROM among the various transfer groups. Limitations, reasons for caution Our retrospective study design may not offer the same level of rigor as a randomized controlled trial. Furthermore, the reproductive database did not provide detailed information on specific endometrial preparation methods (such as hormone replacement therapy or natural cycle), which could potentially influence implantation outcomes. Wider implications of the findings The freeze-all strategy may not be suitable for universal application. When embryos can develop to the blastocyst stage, frozen embryo transfer is a favorable choice, but embryos can only develop to the cleavage stage, fresh embryo transfer becomes a more reasonable option. Trial registration number KMUHIRB-E(I)-20210222

O-207 Comparison of the pregnancy outcomes of transferring frozen embryos versus fresh embryos among advanced maternal age women: a nationwide analysis of 232,942 cycles

Abstract Study question Are there differences in pregnancy outcomes when comparing frozen embryo transfer versus fresh embryo transfer among aged women? Summary answer Frozen embryo transfer yields lower live birth rate for women aged 35-39, but higher rate for women ≥40 compared to fresh embryo transfer. What is known already Advanced maternal age was defined as over 35 years old, while recent literature lifted the threshold to 40. An increasing number of women are postponing childbirth, but reproductive issues become more common after the age of 35, with a significant decline in fertility, particularly after 40, even with IVF. Advanced age affects pregnancy rates, prompting some clinicians to prefer fresh embryo transfer to achieve pregnancy quickly. However, it may be less effective with potential negative effects of ovarian stimulation on endometrial receptivity. Frozen embryo transfer is seen as a better strategy, but data specific to advanced maternal age is lacking. Study design, size, duration This cohort study analyzed the Human Fertilization and Embryology Authority anonymized data from 2011 to 2018 in the United Kingdom. This comprised of a total of 232,942 cycles with advanced maternal age, in which 65,066 patients undergoing frozen embryo transfer cycles, and 167,876 patients undergoing fresh embryo transfer cycles. Participants/materials, setting, methods Data on women with advanced maternal age undergoing IVF/ICSI cycles were analyzed to compare live birth rate and miscarriage rate. The cycles with patients’ age <35, donor oocyte / embryo, PGT, or without embryo to transfer were excluded. Log-binominal regression analysis was performed adjusting for patient age, cause of infertility, number of embryos transferred, year of treatment, and IVF or ICSI cycle. Main results and the role of chance We analyzed data from 232,942 cycles with patients age ≥35, and found that FET cycles exhibited a higher live birth rate than that of fresh embryo transfer cycles (25.5% vs. 24.9%, RR, 1.03; 95% CI, 1.01–1.123). Miscarriage rate (4.6% vs. 3.3%, RR, 1.41; 95% CI, 1.35–1.48) was also different. However, the adjusted RR (aRR) of live birth rate was 0.91; 95% CI, 0.88–0.93, after adjusting for potential confounders. For those patients aged 35-39, live birth rate (28.4% vs. 29.7%, aRR, 0.86; 95% CI, 0.83–0.88) following FET cycles was lower than that of fresh embryo transfer cycles. While FET cycles showed a higher rate of miscarriage (4.6% vs. 3.2%, aRR, 1.83; 95% CI, 1.70–1.98). When patients age≥40, FET cycles showed a higher rate of live birth (18.2% vs. 14.0%, aRR, 1.24; 95% CI, 1.16–1.32) and miscarriage rate (4.7% vs. 3.4%, aRR, 1.72; 95% CI, 1.52–1.94). Besides the live birth rate was sharply decreased than patients aged 35-39 both in FET and fresh embryo transfer cycles. Limitations, reasons for caution The conclusion of the present study might be limited by the anonymous nature of the dataset. Further randomized trials may be required to provide direct evidence for the best embryo transfer strategy for the advanced age women. Wider implications of the findings The study shows that FET exhibited a higher live birth rate in women aged ≥ 40, but lower for those aged 35-39 than fresh embryo transfer. Additionally, FET demonstrated a higher miscarriage rate. Therefore, it is necessary to tailor the embryo transfer strategy for advanced maternal age women. Trial registration number not applicable

P-310 Impact of adenomyosis on the live birth rate during management by in vitro fertilization : a French study

Abstract Study question Evaluate the impact of adenomyosis on the likelihood of live birth after a fresh embryo transfer. Summary answer Adenomyosis reduces the live-birth rate. The location of adenomyosis and the type of protocol appears to have no impact on the live birth rates. What is known already The prevalence of adenomyosis varies between 7 and 27%, and affects 25% of infertile women. Its impact on fertility remains debated. According to some studies, it leads to a lower pregnancy rate, a doubling of the spontaneous miscarriage rate and a lower live birth rate as compared to non-adenomyosis women. However according to some authors adenomyosis does not reduce the live birth rate. Similarly, the impact of the location of adenomyosis remains debated. On the impact of the stimulation protocol, several studies have shown that the use of GnRH agonist improves the live birth rate in patients with adenomyosis. Study design, size, duration This is a retrospective, descriptive and observational study, managed at the fertility department of Dijon University Hospital between January 2015 and March 2020. Systematically, the women infertility cause was assessed. We compared the group of patients with adenomyosis (i.e. symptomatic adenomyosis completed with a 3D ultrasound within a maximum of 1 year prior to management) with controls (i.e. patients treated for another cause of infertility). Ultrasound was performed by the same two experienced operators. Participants/materials, setting, methods We included 340 patients aged 18-41 years. Data concerning live births and type of stimulation protocol were collected from the patient’s electronic medical and therapeutic records. MUSA classification was used to determine whether the adenomyosis was localized or diffuse. The primary endpoint of this study was the live-birth rate (LBR) after fresh embryo transfer. The implantation and miscarriage rates were also compared. Main results and the role of chance We included 92 patients in adenomyosis group, and 248 patients in control group. Baseline characteristics of patients including women age, BMI and smoking habits were comparable in both groups. Moreover, no difference was found on the mean number of mature oocytes and embryos between the two groups. LBR after fresh embryo transfer was significantly lower in the adenomyosis group than in the control (34.8 % versus 41.5%, respectively, p = 0,02). There was no significant difference in implantation rate (35.7% versus 37,4%, p = 0.76). Early miscarriage rate (<12 weeks of amenorrhea) was higher in the control group than the adenomyosis group (15.3 versus 7.5, p = 0.012). Concerning late miscarriage (>12 weeks of amenorrhea), we observed 3 medical termination of pregnancy (all for fetal malformation) and 1 miscarriage (10%) in the adenomyosis group and 1 miscarriage (0.81%) in the control group (p = 0.02). Subgroup analyses showed no decrease in LBR according to adenomyosis location (32.7% versus 37.2% in the diffuse and localized groups, respectively, p = 0.46). Limitations, reasons for caution Even though our cohort is a good reflection of the all-French population of Burgundy since all patients are treated at the fertility center of Dijon. Despite its retrospective nature and the small number of included adenomyosis-patients, the ultrasound scans were performed by two experienced operators that reduced inter-observer variability. Wider implications of the findings It would be useful to carry out a prospective study including more patients to better assess the impact of location on implantation. It would also be interesting to evaluate neonatal and obstetrical complications, especially the late miscarriage issue requiring further investigation. Trial registration number non-clinical trials

O-303 What is the ideal dose of daily FSH after corifollitropin-alfa? A multicentre-randomized control trial

Abstract Study question Does the mean serum trigger-progesterone levels show significant variation based on the administered rFSH dose from day 8 onwards during ovarian stimulation using corifollitropin-alfa? Summary answer Lower rFSH doses from day 8 of ovarian stimulation onwards are linked to reduced serum progesterone (P4) levels without impact on cumulus-oocyte complexes. What is known already Progesterone elevation during ovulation trigger prompts a non-elective freeze-all strategy, given the lower live birth rates in fresh embryo transfers. Ongoing research explores methods to mitigate late follicular phase P4 rise to allow a fresh embryo transfer. Granulosa cells’ progesterone production is an FSH-driven and dose-dependent process, and FSH dose is furthermore pivotal for a good ovarian response. Balancing FSH dose is crucial for both optimal ovarian response and preventing undesirable P4 elevation while maintaining an adequate number of retrieved oocytes and allowing a fresh embryo transfer. Study design, size, duration This study is an interim-analysis of a randomized-controlled multi-center clinical-trial comparing three ovarian-stimulation-protocols: (A) corifollitropin alfa (CFA) followed by rFSH 50 IU/day; (B) CFA followed by rFSH 150 IU/day; (C) CFA followed by rFSH 250 IU/day.The primary outcome is the serum-progesterone-level on the day of hCG among the study groups, secondary outcomes included number of oocytes, clinical pregnancy rates and freeze-all cycles. 167 women (of 261) were randomized between July 2019-November 2023, with a 1:1allocation. Participants/materials, setting, methods Young (<40 years old), normo-ovulatory cycle (25-35 days), with AFC>7 and <20, and a BMI<29 Kg/m2 patients were recruited in the fertility clinic of three different tertiary university hospitals. On day 8 of ovarian stimulation (OS) following CFA administration, patients who needed additional rFSH were randomized into 3 groups (A-B-C). The OS was performed in a GnRH-antagonist protocol and the ovulation triggered with hCG. A fresh embryo-transfer was performed on day 5 following oocyte retrieval. Main results and the role of chance Overall, 167 patients were randomized, 60 in group A, 55 in group B and 52 in group C. The mean age and BMI were comparable between the groups. Mean AMH was respectively 2.2, 2.1 and 2.2 ng/mL, for group A, B and C (p = 0.95). Group A resulted in a significantly lower P4 level at trigger as compared with group B and C (respectively, 0.4ng/mL, 0.9 ng/mL and 1.4 ng/mL; p < 0.001). The mean number of retrieved oocytes was 10.7, 11 and 12.1 for group A, B and C, respectively (p = 0.47), while the mean number of mature oocytes was 7.3, 6.9 and 7.8 for group A, B and C, respectively (p = 0.7). A freeze-all approach was decided for 27%, 29% and 46% for group A, B and C respectively (p = 0.057). No significant differences were found for fresh-embryo-transfer outcomes (chemical pregnancy rates: 33%, 31% and 29%, respectively for A, B and C (p = 0.12).Of interest, comparisons between serum FSH at trigger showed a mean of 12.5, 17 and 20.5 IU/L for group A, B and C, respectively (p < 0.001) while the serum estradiol levels on day of trigger were comparable among the groups (1659, 2092 and 2098 ng/L for group A, B and C, respectively (p = 0.091). Limitations, reasons for caution This is an interim analysis planned to detect the mean difference in COC between groups. Therefore, the mean differences of the primary outcome should be interpreted as exploratory findings which warrant future investigation. Wider implications of the findings Administering a lower rFSH dose from day 8 onward during ovarian stimulation results in comparable numbers of COC but also leads to significantly lower serum P4 levels. Consequently, this finding has the potential to reduce the overall consumption of rFSH, thereby possibly increasing the likelihood of a fresh embryo transfer. Trial registration number NCT03686852

P-579 Is the use of donated oocytes effective to reestablish live birth rates? Reproductive outcomes of 5313 euploid embryo transfers in autologous versus egg donation cycles

Abstract Study question Is live birth rate of autologous versus donor cycles similar after a euploid embryo transfer? Summary answer The live birth rate was significantly higher in autologous cycles after a euploid embryo transfer. What is known already Advanced maternal age (AMA) is a detrimental factor for patients to achieve a successful outcome in ART. Physiological ovarian aging negatively affects oocyte quality and quantity. Thus, the number of cycles with donated oocytes is increasing for AMA patients worldwide, with the perspective of surpass the oocyte factor and achieve a live birth in similar rates as younger patients. The goal of this study was to compare the live birth rates of autologous versus donor cycles after a euploid embryo transfer. Study design, size, duration Observational cohort study including all patients of IVF cycles with a euploid embryo transfer after PGT-A (NGS technology), according to medical referral between Jan/2016 and Dec/2020 (n = 3623 patients and 4025 cycles) in a private ART center. Participants/materials, setting, methods Reproductive outcomes between autologous and egg donation cycles were compared and data were analyzed in the follow subgroups: cycles with a fresh oocyte and fresh embryo transfer (FRESH), frozen embryo transfer (FET) and fresh embryo transfer from frozen oocytes (FOT). Positive pregnancy test (PPT), clinical pregnancy (CP), clinical miscarriage (CM) and live birth (LB) rates were compared. Kruskal-Wallis and Fisher test were applied for statistical analysis, significance was considered if p < 0,05. Main results and the role of chance In total, 3623 patients – 88.9% autologous and 11.1% with donated oocytes – were included. They performed 4025 ETs (3591/434) with 5313 biopsied blastocysts (4736/577) in a mean of 1,32/1,33 blastocysts per transfer in autologous/donated cycles respectively. The majority of patients using autologous and donated oocytes underwent a FET (97,2% and 63,1%), followed by FOT (1,5% and 34,7%) and FRESH (1,3% and 2,2%, respectively). Mean maternal age in autologous and donor cycles was 37,76±3,9yo and 43,47±4,26yo and oocyte donors were 24,99±3,86yo. In subgroups, autologous patients in FRESH were 38,33±2,69 yo, similar in FET (37,73±3,93 yo) and older in FOT, 39,25±3,93 yo (p = 0,03). Patients in donor cycles showed no difference in age. PPT and CP were similar in autologous and donated cycles (PPT: 59,2% vs 54,8%, p = 0.08; CP: 52,2% vs 48,2%, p = 0.11). In subgroup analysis, PPT and CP were higher in donated cycles vs autologous cycles for FOT (PPT: 50,7% vs 33,3%, p = 0.004; CP: 40,7% vs 20,8%, p = 0.01). Overall, CM were higher in donated cycles (15,5% vs 10,6%, p = 0.03), especially after FET (16,8% vs 10,6%, p = 0.025). LB rates were higher in autologous compared to donated cycles (37,8% vs 29,5%, p = 0.0007). There was no significant difference in LB rates in subgroup analysis. Limitations, reasons for caution This is a large cohort study; however, we cannot exclude potential bias due its retrospective nature. Including only euploid embryos, we excluded bias on ploidy status when comparing autologous versus donated oocytes cycles, yet the potential harmful of embryo biopsy may not be neglect. Wider implications of the findings Live birth rate was significantly higher in autologous cycles after a euploid embryo transfer, regardless of subgroups. AMA patients that choose to undergo an IVF treatment with donated oocytes should be aware that there are other important factors related to a successful reproductive outcome, including immunological adaptation and endometrial aging. Trial registration number Not applicable.