Number Of Transferred Embryos Research Articles

Reproductive outcomes of dual trigger therapy with GnRH agonist and hCG versus hCG trigger in women with diminished ovarian reserve: a retrospective study

BackgroundDiminished ovarian reserve (DOR) is one of the obstacles affecting the reproductive outcomes of patients receiving assisted reproductive therapy. The purpose of this study was to investigate whether dual trigger, including gonadotropin‐releasing hormone agonist (GnRHa) and human chorionic gonadotropin (hCG), can improve pregnancy outcomes in patients with DOR undergoing in vitro fertilization (IVF) cycles using mild stimulation protocols.MethodsA total of 734 patients with DOR were included in this retrospective study. Patients were divided into a recombinant hCG trigger group and a dual trigger group (hCG combined with GnRHa) according to the different trigger drugs used. The main outcome measures included the number of oocytes retrieved, the fertilization rate, the number of transferable embryos, the implantation rate, the clinical pregnancy rate, the miscarriage rate, the live birth rate (LBR), and the cumulative live birth rate (CLBR). Generalized linear model and logistic regression analyses were performed for confounding factors.ResultsThere were 337 cycles with a single hCG trigger and 397 cycles with dual trigger. The dual trigger group demonstrated significantly higher numbers of retrieved oocytes [3.60 vs. 2.39, adjusted β = 0.538 (0.221–0.855)], fertilized oocytes [2.55 vs. 1.94, adjusted β = 0.277 (0.031–0.523)] and transferable embryos [1.22 vs. 0.95, adjusted β = 0.162 (-0.005–0.329)] than did the hCG trigger group, whereas no significant difference in the fertilization rate was observed between the two groups. Moreover, the embryo transfer cancellation rate (35.5% vs. 43.9%) was obviously lower in the dual trigger group. Among the fresh embryo transfer cycles, the implantation rate, clinical pregnancy rate, miscarriage rate and live birth rate were similar between the two groups. After controlling for potential confounding variables, the trigger method was identified as an independent factor affecting the number of oocytes retrieved but had no significant impact on the CLBR.ConclusionsDual triggering of final oocyte maturation with hCG combined with GnRHa can significantly increase the number of oocytes retrieved in patients with DOR but has no improvement effect on the implantation rate, clinical pregnancy rate or LBR of fresh cycles or on the CLBR.

Evaluation of Nanopore Sequencing on Polar Bodies for Routine Pre-Implantation Genetic Testing for Aneuploidy.

Preimplantation genetic testing for aneuploidy (PGT-A) using polar body (PB) biopsy offers a clinical benefit by reducing the number of embryo transfers and miscarriage rates but is currently not cost-efficient. Nanopore sequencing technology opens possibilities by providing cost-efficient and fast sequencing results with uncomplicated sample preparation work flows. In this comparative experimental study, 102 pooled PB samples (99 passing QC) from 20 patients were analyzed for aneuploidy using nanopore sequencing technology and compared with array comparative genomic hybridization (aCGH) results generated as part of the clinical routine. Samples were sequenced on a Nanopore MinION machine. Whole-chromosome copy-numbers were called by custom bioinformatic analysis software. Automatically called results were compared to aCGH results. Overall, 96/99 samples were consistently detected as euploid or aneuploid in both methods (concordance = 97.0%, sensitivity = 0.957, specificity = 1.0, positive predictive value = 1.0, negative predictive value = 0.906). On the chromosomal level, concordance reached 98.7%. Chromosomal aneuploidies analyzed in this trial covered all 23 chromosomes with 98 trisomies, and 97 monosomies in 70 aCGH samples.The whole nanopore work flow is feasible in under 5 h (for one sample) with a maximum time of 16 h (for 12 samples), enabling fresh PB-euploid embryo transfer. A material cost of US$ 165 (EUR 150)/sample possibly enables cost-efficient aneuploidy screening. This is the first study systematically comparing nanopore sequencing with standard methods for the detection of PB aneuploidy. High concordance rates confirmed the feasibility of nanopore technology for this application. Additionally, the fast and cost-efficient work flow reveals the clinical utility of this technology, making it clinically attractive for PB PGT-A.

Aneuploidy in Oocytes From Women of Advanced Maternal Age: Analysis of the Causal Meiotic Errors and Impact on Embryo Development

ABSTRACT Many chromosome abnormalities are commonly observed and can lead to early pregnancy loss, miscarriage, or the birth of children with chromosomal defects. Such abnormalities are considered a major factor in the low pregnancy rate after assisted reproductive technology and natural conception. Preimplantation genetic testing for aneuploidy (PGT-A) aims to minimize the transfer of aneuploid embryos. Embryonic aneuploidies arising from errors in meiosis have an incidence of approximately 25% in embryos from women younger than 35 years, to more than half in embryos from women aged older than 35 years. Although these embryos are able to develop to the blastocyst stage, they tend to be of lower morphological quality. A recent multicenter randomized clinical trial (ESTEEM) analyzed polar bodies (PBs) from women after intracytoplasmic sperm injection aged between 36 and 40 years using microarrays in 205 cycles and found that the transfer of embryos from euploid oocytes did not lead to a higher live birth rate but was associated with a reduction in the number of embryo transfers and miscarriages. This study aimed to evaluate all PB results from this RCT and characterize the types of chromosomal abnormalities and the chromosomes most frequently affected. The ESTEEM trial obtained biopsy of first (PB1) and second (PB2) PB in the cohort receiving PGT-A and analyzed them using array comparative genomic hybridization (aCGH). A total of 693 PB pairs had full results available, including 676 confirmed fertilized oocytes. Chromosome segregations, including likely underlying mechanisms, from these pairs are reported here. To estimate the reliability of the aCGH procedure, 72 PB pairs from a single center were reanalyzed using next-generation sequencing (NGS). Embryos were classified into 4 categories based on morphology: good, fair, poor, and degenerated. A comparative analysis was performed to assess the association between chromosome status and embryo quality as well as study group (PGT-A vs control) and embryo quality. A total of 213/676 oocytes were euploid and 413/676 were aneuploid, whereas in the remaining 50 oocytes, an abnormality observed in PB1 was compensated by an abnormality in PB2. A total of 693 PB pairs reported chromatic numbers with results for 15,939 chromosomes. An abnormal segregation, in PB1 and/or PB2, was observed in 1162 chromosomes (7.3%) in 461 PB pairs. Chromosomes 22 (16.7%), 16 (16.6%), 19 (14.4%), 21 (13.7%), and 15 (12.4%) had the highest frequencies for abnormal segregations. The abnormal segregations were compatible with precocious separation of sister chromatids in meiosis 1 (M1) (n = 568; 48.9%), nondisjunction of chromatics in meiosis 2 (M2) or reverse segregation (n = 417; 35.9%), and nondisjunction in M1 (n = 65; 5.6%). However, 112 chromosomes had segregation patterns that could not be categorized into 1 of the 9 known mechanisms causing aneuploidy in oocytes. Concordance between aCGH and NGS was obtained for both PBs for 1650 of 1656 analyzed chromosomes (99.6%). Embryos predicted to be aneuploid had significantly worse quality scores on day 3 (adjusted odds ratio [aOR], 0.62; 95% confidence interval [CI], 0.43–0.90), day 4 (aOR, 0.15; 95% CI, 0.06–0.39), and day 5 (aOR, 0.28; 95% CI, 0.14–0.58). This study represents one of the largest analyses of chromosomal copy number in both PBs to date and highlights the frequent unexplained chromosome copy numbers underscoring the gap of knowledge into the mechanisms causing aneuploidy in oocytes.

The efficacy of platelet rich plasma on women with poor ovarian response: a systematic review and meta-analysis

Background Platelet-rich plasma (PRP) is a therapeutic approach that is gaining attention for its potential in the treatment of poor ovarian response. This meta-analysis aimed to systematically review and analyze clinical studies to evaluate the impact of PRP on poor responders undergoing ovarian stimulation for IVF. Methods A comprehensive search was conducted in electronic databases, including PubMed, Embase, Scopus, Web of Science, and the Cochrane Library to identify relevant studies published in English. The pooled data, such as pregnancy outcome, number of MII oocytes, number of transferable embryos, and ovarian reserve markers were analyzed using R version 4.2.3. Results A total of 10 trials were enrolled in the present meta-analysis. Following PRP treatment, live birth rate was found to be 16.6% (95% CI 8.8%-26.1%), while clinical pregnancy rate was observed to be 25.4% (95% CI 13.1%-39.9%). PRP pretreatment resulted in a higher number of MII oocytes (MD 1.073, 95% CI 0.720 to 1.427), a higher number of embryos (MD 0.946, 95% CI 0.569 to 1.323), a higher antral follicle count (MD 1.117; 95% CI 0.689 to 1.544), and the change of hormone levels. Conclusions Among the studies evaluated in this review, PRP showed promising results in poor responder. Further research is required to clarify the potential role of PRP in female reproductive health.

Risk factors of ectopic pregnancy after in vitro fertilization-embryo transfer in Chinese population: A meta-analysis.

The prevalence of ectopic pregnancy after assisted reproduction is notably high, posing a significant threat to the life safety of pregnant women. Discrepancies in published results and the lack of a comprehensive description of all risk factors have led to ongoing uncertainties concerning ectopic pregnancy after assisted reproduction. This study aimed to understand the risk factors for ectopic pregnancy after in vitro fertilization-embryo transfer in the Chinese population and provide a reference for targeted prevention and treatment. A comprehensive search of the China National Knowledge Infrastructure, Wang fang Database, China Science Technology Journal Database, Chinese Biomedical Literature Database, PubMed, Web of Science, and Embase was conducted to identify relevant literature on the risk factors for ectopic pregnancy in Chinese women after assisted reproductive technology in Chinese women. A meta-analysis of the included studies was performed using Stata17. Overall, 34 articles were included in the analysis. The risk factors for ectopic pregnancy after in vitro fertilization-embryo transfer in the Chinese population included a thin endometrium on the day of HCG administration and embryo transplantation, a history of ectopic pregnancy, secondary infertility, a history of induced abortion, polycystic ovary syndrome, decreased ovarian reserve, tubal factor infertility, cleavage stage embryo transfer, fresh embryo transfer, artificial cycle protocols, elevated estradiol levels on the day of human chorionic gonadotropin administration, a history of tubal surgery, two or more number of embryo transfers, previous pregnancy history, and a history of pelvic surgery. This study clarified the factors influencing ectopic pregnancy after in vitro fertilization and embryo transfer in the Chinese population, focusing on high-risk groups. Targeted and personalized intervention measures should be adopted to prevent and detect the disease early to reduce its incidence and harm. The protocol for this view was registered in PROSPERO (CRD42023414710).

Analyzing the dynamic measurement of growth and development in children born after the transplantation of poor quality blastocyst embryos: a propensity matching study

Objective This study aimed to observe the dynamic measurement of growth and development in children (0–3 years) after transplantation of low-quality frozen-thawed single blastocysts. Methods This was a retrospective cohort study conducted from January 2016 to December 2019 at a single center. The follow-up data of the children were obtained from the Jiangsu Province Maternal and Child Database. A total of 350 singleton live births were included. Based on the blastocyst score, the live births were divided into good-quality blastocyst embryo (GQE) group (315 live births) and poor-quality blastocyst embryo (PQE) group (35 live births). To improve statistical efficiency and control for potential confounding factors, singletons conceived from PQEs were matched with a 3:1 ratio according to couple ages, BMI, occupation and women AMH levels. Ultimately, 32 children in the PQE group and 95 children (with one missing data) in the GQE group were included in the final analysis. Results After matching for parents’ age, BMI, occupation and maternal serum AMH level, there was no significant difference in growth and development of children between the PQE group and GQE group. However, the E2 level on trigger days, the rate of 2PN oocyte, and blastocyst formation rate in the PQE group were significantly lower than in the GQE group (p < .05). The number of embryo transfers (ETs) in the PQE group was higher than in the GQE group (p < .0001). The rate of cesarean section in the PQE group was significantly higher than in the GQE group (p < .05). The height (at 3 months) and head circumference (at 12 months) in the PQE group were lower than in the GQE group (p < .05). Conclusions Transplantation of PQEs did not affect the growth and development of offspring (0–3 years) compared to good-quality blastocysts. However, the oocyte and embryo development potential was lower in the PQE group than in the GQE group. These results provide clinical reference that the transfer of PQE could be acceptable for patients with only PQE embryos.

Analysis of controlled ovarian hyperstimulation protocols in women over 35 years old with poor ovarian response: a real-world study

The objective of this study was to investigate the optimal controlled ovarian hyperstimulation (COH) protocol for patients aged 35 and above with poor ovarian response (POR), utilizing real-world data. This retrospective cohort study examined clinical information from a total of 4256 patients between January 2017 and November 2022. The patients were categorized into three groups: modified GnRH agonist protocol (2116 patients), GnRH antagonist protocol (1628 patients), and Mild stimulation protocol (512 patients). Comparative analysis was conducted on clinical variables and pregnancy outcomes across the three groups. The GnRH agonist protocol was associated with a higher number of oocyte number (4.02 ± 2.25 vs. 3.15 ± 1.52 vs. 2.40 ± 1.26, p < 0.001), higher number of transferable embryos (1.73 ± 1.02 vs. 1.35 ± 1.22 vs. 1.10 ± 0.86, p = 0.016), higher cumulative live birth rate 28.50(603/2116) vs. 24.94(406/1628) vs. 20.51(105/512), p < 0.001) than GnRH antagonist protocol and Mild stimulation protocol, the Mild stimulation protocol was associated with a higher miscarriage rates 16.27(62/381) vs. 16.61(48/289) vs. 32.22(29/90), p = 0.001) than the other two groups. Therefore, it can be concluded that all three protocols can be used in patients over 35 years old with poor ovarian response. However, if patients require more frozen-thawed embryo transfers to achieve better cumulative live birth rates, the modified GnRH agonist protocol may be the preferable option.

Benefits of Blastocyst Transfer With at Least Three Good-Quality Cleavage-stage Embryos in Women of Advanced Maternal Age: A Retrospective Analysis

ObjectivesLimited studies on the benefits of blastocyst transfer in advanced maternal age (AMA) (≥40 years) have been reported. Our objective was to find whether blastocyst-stage embryo transfer improves pregnancy and live birth rates in women ≥40 years who have 3 or more good-quality cleavage-stage embryos. MethodsAll fresh in vitro fertilization-intracytoplasmic sperm injection cycles performed from January 2020 to December 2021 in AMA women that progressed to transfer were considered for analysis. We compared fresh and cumulative ongoing pregnancy rates in AMA women of those who had a cleavage-stage transfer, while meeting the criteria for extended culture (≥3 high-quality embryos, group 1), and those who underwent blastocyst transfer (group 2). Demographic parameters, stimulation, embryology, fresh and cumulative ongoing pregnancy rates, and clinical miscarriage rates were compared. ResultsDuring the study period, 255 cycles were analyzed including group 1 (n = 99) and group 2 (n = 156). Group 1 participants were older and had a greater number of embryos for transfer. Fresh and cumulative ongoing pregnancy rates per transfer were higher in group 2 compared to group 1 (23.4% vs. 13.1%, P = 0.04; 25.5% vs. 14.1%, P = 0.03), while overall miscarriage rates were higher in group 1 than group 2 (51.7% vs. 25%, P = 0.01). ConclusionsBlastocyst culture provides a benefit to AMA women who have at least 3 good-quality embryos on day 3 resulting in significantly higher fresh and cumulative ongoing pregnancy rates and lower miscarriage compared to cleavage-stage transfers.

Embryo yield and quality in superovulated Simmental donor cows following oral supplementation with different sources of omega-3 and omega-6 fatty acids

Owing to contradictory results with respect to the yield and quality of embryos after supplementation with omega-3 fatty acids, this study sought to determine the effect of an oral supplement containing sources of omega-3 and omega-6 fatty acids on the ovarian response and embryo quality after superovulation. Cows were allocated to receive one of three oral supplement regimens. In the control (CO) group (n = 9), cows were fed a control supplement without fatty acids. The cows in the soybean oil (SO) (n = 8) and linseed oil (LO) (n = 8) groups received supplements containing SO or LO, respectively. Supplements were administered for 28 days, commencing 7 days before the onset of estrus synchronization until the day of embryo collection. The estrous cycle of all cows was synchronized by inserting a controlled internal drug release (CIDR) device (progesterone 1.38 g), followed by the administration of estradiol benzoate 2.5 mg. The CIDR device was withdrawn 7 days after insertion, followed by intramuscular administration of dinoprost 25 mg. Superovulation was induced via the administration of 152 mg of follicle-stimulating hormone (Folltropin-V) in tapered doses, starting 72 h before CIDR withdrawal. The embryos were collected 6 days after artificial insemination. The estrous response, onset of estrus after CIDR withdrawal, and number of ovulations were similar among the experimental groups (p > 0.05). The mean number of transferable embryos (grades 1 and 2) was higher in the LO group compared to the CO group (9.0 vs 3.2; p < 0.05). Although the number of transferable embryos (grades 1 and 2) was greater in the LO group than that in the SO group, the difference was not statistically significant (9.0 and 4.4; p > 0.05). In conclusion, oral supplementation with LO for 28 days increased the yield of transferable embryos, which could potentially improve the profitability of embryo transfer programs in cattle.

Decreased pregnancy rate per embryo transfer in women undergoing assisted reproductive technology after abdominal trachelectomy: A retrospective study

ObjectiveAbdominal trachelectomy (AT) is a fertility-preservation surgery for patients with early-stage cervical cancer. Few studies have reported the outcomes of assisted reproductive technology (ART) in patients after AT. The aim of this study was to evaluate the outcomes of ART after AT. Study DesignIn this retrospective study, we compared the ART outcomes of 13 patients who underwent AT at another hospital prior to undergoing ART at our clinic (T group) and 52 control patients (non-T group) who did not undergo AT prior to ART, selected on the basis of age, time of treatment onset, and serum anti-Müllerian hormone concentrations, matched 1:4, respectively. ResultsCumulative live birth rates were 62% (8/13) and 65% (34/52) in the T and non-T groups, respectively (p = 0.795). The total number of oocyte retrieval cycles was 34 in the T group and 95 in the non-T group. In all oocyte retrieval cycles, no significant differences were noted in the number of oocyte retrievals, rate of fertilization, and presence of good-quality blastocysts (Gardner classification ≥ BB). The total number of embryo transfer (ET) cycles was 55 in the T group and 109 in the non-T group. The pregnancy and live birth rates per ET were lower in the T group than those in the non-T group (pregnancy rate, 20% vs. 39%, p = 0.017; live birth rate, 15% vs. 30%, p = 0.028; respectively). Endometrial thickness before ET was lower in the T group vs. the non-T group: median (range): 7.4 (3.5–14.3) mm vs. 9.0 (5.5–14.9) mm, respectively; p < 0.0001. Multivariate logistic regression models showed that age at oocyte retrieval (adjusted odds ratio [OR], 0.76; 95% confidence interval [CI], 0.66–0.87), use of good-quality blastocysts (adjusted OR, 3.23; 95% CI, 1.20–8.67), and history of AT (adjusted OR, 0.28; 95% CI, 0.11–0.72) were associated with the pregnancy rate per ET. ConclusionThe pregnancy rate per ET was lower in patients with vs. without a history of AT. Clinicians should be aware of the longer time to pregnancy in patients who undergo ART after AT.

P-518 The effect of inactivated SARS-CoV-2 vaccination on the outcome of the first frozen-thawed embryo transfer cycle

Abstract Study question Is there an effect of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination on the outcome of the first frozen-thawed embryo transfer(FET) cycle. Summary answer Inactivated SARS-CoV-2 vaccination did not affect the outcome of the first FET cycle, including clinical pregnancy rate, early miscarriage rate and newborns’ birth weight. What is known already SARS-CoV-2 vaccination can significantly reduce the risk of severe disease and death after SARS-CoV-2 infection. However, due to the lack of vaccine safety data, the infertile population who plan to undergo ART treatment have high concerns about the safety of vaccine vaccination. To date, there are merely few researches aimed to determine the impact of inactivated SARS-CoV-2 vaccination on reproductive and neonatal outcomes of women attempting FET. Study design, size, duration This was a retrospective cohort study of patients who underwent the first FET cycle in the Reproductive Center of Ningbo Women and Children Hospital from November 1st 2021 to December 19th 2022. All patients were followed up until January 19th 2023. Patients whose age was &amp;gt;40 years old were excluded. The patients were organized into groups based on age, anti-Müllerian hormone (AMH) levels, antral follicle count (AFC), body mass index (BMI), and vaccination or not. Participants/materials, setting, methods Patients fully vaccinated with two doses of Sinopharm or Sinovac inactivated vaccines(Group A, n = 452) were compared with unvaccinated patients(Group B, n = 452) who were matched by age, AMH, AFC and BMI. The baseline characteristics and clinical outcomes of each group were compared.SPSS version 26.0 (SPSS Inc., USA) was used for all data analyses. Main results and the role of chance There were no statistically significant differences in age, AMH, AFC, BMI, infertility duration, infertility type, infertility causes, fertilization type, ovarian stimulation protocol, number of oocytes retrieved(9.24 vs 9.92, p = 0.102), endometrial preparation protocol, endometrial thickness(9.40 vs 9.29mm, p = 0.344), embryo stage, number of embryos for transfer(1.4 vs 1.42, p = 0.589) between two groups. No difference was found between vaccinated and unvaccinated patients in clinical pregnancy rate(55.31% vs 57.52%, p = 0.502), early miscarriage rate(10.4% vs 11.54%, p = 0.681). The newborns’ birth weight were comparable between two groups(2971.44 vs 3156.83g, p = 0.66). Limitations, reasons for caution This is a single-center retrospective study and further accumulated data is warranted to validate the findings. Because of the short follow-up time, some patients are still pregnant, hence we await live birth outcomes. Wider implications of the findings These findings contribute to the evidence regarding the reproductive safety of inactivated SARS-CoV-2 vaccination for fertility-seeking women, and it can provide further theoretical reassurance for doctors and patients to vaccinate before pregnancy. Trial registration number not applicable

P-237 In vitro time to maturation of Metaphase I oocytes: a time-lapse study correlating blastocyst formation and ploidy status

Abstract Study question What is the impact of metaphase I (MI) time to mature period (TTM) regarding blastocyst development and ploidy status? Summary answer A short period of TTM (0.1 to 1.0) is related to an increase number of blastocyst formation when compared to longer TTM (1.1 to 3.0). What is known already To achieve meiotic competence, coordinated nuclear and cytoplasmic changes must occur in the oocyte to support fertilization and DNA replication and to ensure correct ploidy of the zygote and embryonic genome activation. Concomitant with chromosome condensation and migration, oocyte maturation goes by cytoplasm reorganization throughout the transitions of MI, polar body extrusion and MII. Despite the optimization of COH protocols, nearly 20% of the retrieved oocytes remain immature at the GV or MI stages. In vitro maturation of MI could increase the number of available embryos; however, longer culture time may affect oocyte quality, resulting in abnormal fertilization and cleavage. Study design, size, duration Prospective cohort study from 244 patients (n = 277 cycles) that had at least 1 MI oocyte after oocyte retrieval (OPU) following controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF) treatment according to medical referral in an single private ART center from January/2019 to November/2022. All MI oocytes were placed in a time-lapse incubator (TL, EmbryoScope, Vitrolife, Sweden) to check the exact time of first polar body extrusion (TTM to MII) before intracytoplasmic sperm injection (ICSI). Participants/materials, setting, methods Three hours after OPU, oocytes were denuded and assessed for maturation. Six-hundred and seven MI oocytes were followed in TL and those that reached the MII stage in a maximum of 6 hours post-OPU, were injected by ICSI (at 6h post-OPU) and stratified according to the TTM (0.1-1.0 hours and 1.1-3.0 hours). Fertilization rate, blastocyst formation, and ploidy were assessed. Kruskal-Wallis, chi-squared and Fisher tests were applied for statistical analysis. p &amp;lt; 0,05 was considered significant. Main results and the role of chance Patient mean age (n = 244) was 38,50 ± 3,40 years. From those, 25 patients (10.3%) had 2 cycles and 4 patients (1.6%) had 3 cycles with at least 1 MI oocyte. Age, anti-Müllerian hormone (AMH), #OPU, #MII, %MII (MII/OPU), #MI and MI% (MI/OPU) mean were not statistically different in patients with 1, 2 or 3 cycles in our cohort. One hundred forty-nine patients (61%) in 165 cycles (59.6%) had at least 1 oocyte that reached MII stage. In total, 248 oocytes were injected after 0.1-1.0h (group 1, n = 104, 41.9%) and 1.1-3.0h (group 2, n = 144 oocytes, 58.1%) of in vitro maturation. Age (38,99 ± 3,01 vs 38,85 ± 3,31), AMH (1,27 ± 1,29 vs 1,63 ± 1,87), #OPU (8,98 ± 4,32 vs 8,90 ± 4,34), #MII (4,41 ± 2,74 vs 4,44 ± 2,178), %MII (47.6% ± 18.8% vs 48.4% ± 17.1%) and %MI that followed to ICSI (59.2% ± 28.5% vs 54.8% ± 29.2%) were not different between groups 1 and 2 respectively. The mean number of MI that followed to ICSI were higher in group 1 (1,28 ± 0,48 vs 1,10 ± 0,32, p = 0.0008). Normal fertilization (2PN) and embryo cleavage were similar between groups (54.8% vs 45.1%, p = 0.157, 96.6% vs 93.3%, p = 0.467, respectively). However, blastocyst formation rate (#blastocyst/#fertilized) was higher in group 1 (n = 33, 55.9% vs n = 26, 34.7%, p = 0.015). Euploidy rates were similar between groups (9/28, 32% vs 4/24, 16%, p = 0.336). Limitations, reasons for caution Besides the retrospective nature of this study, male factor and infertility reason were not considered in this analysis. Due to the low number of blastocyst formation and consequentially ploidy assessment and number of embryo transfer, the results regarding euploidy rate may be underestimated and pregnancy rates were not included. Wider implications of the findings Oocytes that reached maturity up to 1 hour after denudation showed higher blastocyst formation rate, thus increasing embryo availability to transfer. In vitro-matured oocytes exhibit increased spindle and chromosomal abnormalities compared with oocytes matured in vivo, which may explain the lower rates of euploid embryos, especially in group 2. Trial registration number Not applicable.

O-100 Recurrent implantation failure

Abstract Study question How should Recurrent Implantation Failure (RIF) in ART patients be defined and managed? Summary answer This is the first ESHRE good practice recommendations paper providing a definition for RIF and guidance on how to investigate causes and contributing factors and how to improve the chances of a pregnancy. What is known already RIF is a challenge in the ART Clinic, with a multitude of investigations and interventions offered and applied in clinical practice, often without biological rational or unequivocal evidence of benefit. Study design, size, duration This recommendations document was developed according to a predefined methodology for ESHRE good practice recommendations. Recommendations are supported by data from the literature, if available, the results of a previously published survey on clinical practice in RIF and the expertise of the working group. A literature search was performed in PubMed and Cochrane focusing on “recurrent reproductive failure", "recurrent implantation failure" and "repeated implantation failure“. Participants/materials, setting, methods The ESHRE RIF Working Group included 8 members representing the ESHRE Special Interest Groups of Implantation and Early Pregnancy, Reproductive Endocrinology, and Embryology, and completed with an independent chair and an expert in statistics. The recommendations for clinical practice were formulated based on the expert opinion of the Working Group, while taking into consideration the published data and results of the survey on uptake in clinical practice. The draft document was then opened for online peer review to ESHRE members and revised in light of the comments received. Main results and the role of chance RIF describes the scenario in which the transfer of embryos considered to be viable has failed to result in a positive pregnancy test sufficiently often in a specific patient to warrant consideration of further investigations and/or interventions. The recommended threshold for the cumulative predicted chance of implantation to identify RIF for the purposes of initiating further investigation is 60%. When a couple have not had a successful implantation by a certain number of embryo transfers and the cumulative predicted chance of implantation associated with that number is greater than 60%, then they should be counselled on further investigation and/or treatment options. This term defines clinical RIF for which further actions should be considered. Nineteen recommendations were formulated on investigations when RIF is suspected, and 13 on interventions. Limitations, reason for caution While awaiting the results of further studies and trials, the ESHRE Working group recommends identifying of RIF based on the chance of successful implantation for the individual patient or couple and to restrict investigations and treatments to those supported by a clear rationale and data indicating their likely benefit. Wider implications of the findings This paper provides good practice advise, but also highlights the investigations and interventions that need further research. This research, when well-conducted, will be key to making progress in the clinical management of RIF. Study funding and competing interest(s) Yes. The other authors had nothing to disclose.

P-456 Economic evaluations of assisted reproductive technology in high income countries - a systematic review

Abstract Study question In high-income country settings, what is the evidence supporting economic evaluations of in vitro fertilisation (IVF) interventions? Summary answer Most interventions associated with IVF are high cost for minimal improvement in effectiveness, leading to excessively high acceptability thresholds. What is known already The economic burden of infertility, and approaches to reduce costs and increase access have been identified in the top 10 research priorities for future infertility research. Meanwhile, there has been exponential growth in use of ART for infertility, especially in high-income countries. Therefore, it is important to map the landscape of economic evaluations in IVF research to inform health policy and future research. Study design, size, duration A systematic review of studies of an IVF intervention together with an economic evaluation conducted in high income countries between 2011 and 2022 was completed. Seven electronic databases were searched for eligible studies (MEDLINE, PUBMED, EMBASE, COCHRANE, ECONLIT, SCOPUS or CINAHL). Participants/materials, setting, methods Studies assessing a component of IVF with a cost effectiveness, cost benefit, cost utility or cost minimization assessment were included. Studies were examined to assess their chosen outcome measure, perspective, completeness of reporting and cost effectiveness of the intervention studied. Cost data were converted to USD, taking inflation into consideration. Main results and the role of chance Of the 40 included studies, 62% evaluated an unselected population and 68% used livebirth as the effectiveness outcome measure. Modelling studies predominated (65%) over those alongside trials. Most (80%) spoke from a health funder perspective. There were 11 IVF interventions assessed together with an economic evaluation. The incremental cost effectiveness ratio was greatest for those interventions where the intervention did not improve efficacy significantly. The intervention of PGT-A was assessed as either less effective and more expensive, or more effective, but costing up to $600,000 USD for each additional livebirth. Likewise, intracytoplasmic sperm injection for non-male factor infertility, conferred minimal benefit but cost up to $72000 USD per additional livebirth. Choice of agents for ovarian hyperstimulation were assessed in 15 included papers. Recombinant FSH is more effective and slightly more expensive than biosimilars. The direction of effect of the cost effectiveness findings was the same for the groups of studies assessing IVF, ICSI, PGT-A and embryo transfer number, increasing confidence in the findings across different settings and funding models. Limitations, reasons for caution Systematic reviews of economic evidence rely on assumptions of evidence in included studies. The data on health outcomes (e.g. pregnancy rates) were sometimes optimistic compared with findings in evidence from large trials or systematic reviews. There is variable reporting quality which might increase uncertainty around the cost effectiveness results. Wider implications of the findings Economic evaluation of IVF interventions is important for state funders and individuals who pay for treatment. Awareness of the real price per outcome allows consideration for funding to be applied more effectively. Multi-faceted decision making is needed. Cost effectiveness alone should not champion interventions that may otherwise have adverse consequences. Trial registration number not applicable

P-679 Controlled ovarian stimulation using follitropin delta results in higher cumulative live birth rate compared to follitropin alfa/beta in a large prospective real world dataset

Abstract Study question Does IVF/ICSI-treatment using follitropin delta (hrFSH) result in higher pregnancy rates (PR) or live birth rates (LBR) compared to follitropin alfa/beta (recFSH)? Summary answer Real world data (RWD) from a large prospective German registry study shows that using hrFSH results in higher pregnancy rates compared to recFSH. What is known already Follitropin delta represents a new recombinant FSH derived from a human cell line. Contrary to follitropin alfa or beta, follitropin delta has a glycolysation pattern consisting of α2,3- and α2,6-linked sialic acids which is more similar to native human FSH. Follitropin delta is approved for use with an individualized dosing algorithm based on serum AMH and body weight, targeting an optimal ovarian response (8-14 oocytes). Efficacy and safety have been demonstrated in numerous clinical trials. Moreover, Follitropin delta seems to reduce the risk of OHSS although its safety with respect to ovarian hyperstimulation using RWD remains to be investigated. Study design, size, duration The German IVF Registry collects prospectively data about IVF/ICSI-treatments from 140 German IVF centers. The underlying analysis of RWD includes controlled ovarian hyperstimulation cycles that have been performed in Germany between 2017-2021. Study groups were built subject to the gonadotropin used for stimulation, irrespective of previous treatments: (1) hrFSH, n = 3002, (2) recFSH, n = 135293. “Pregnancy” was defined as clinically assessed, intrauterine pregnancy, including miscarriages. Biochemical pregnancies were not defined as “pregnant”. Ectopic pregnancies (n = 558) were excluded. Participants/materials, setting, methods PR and LBR were calculated subject to the number of embryo transfers (ET) (n = 2062 (rFSH) vs. n = 103357 (recFSH)) after excluding freeze-all cycles, (n = 529 (hrFSH) vs. n = 13682 (recFSH)) and cycles that ended without ET (n = 411 (hrFSH) vs. n = 18254 (recFSH)). The collected data were saved in compliance with the applicable data processing regulations. Statistical analysis was performed using Fishers-exact- and students-t-test and Microsoft Excel, whereas p &amp;lt; 0.05 was defined as significant. Main results and the role of chance There was no difference between the study groups regarding age (33.9 ± 4.00y (hrFSH) vs. 33.8y±4.34y (recFSH), p = 0.12) or infertility diagnosis. Stimulation with hrFSH resulted in a higher number of oocytes (11.15±7.2 vs. 10.39±7.01, p &amp;lt; 0.01). Antagonist protocol was used less often in the hrFSH-group (78% (2344/3002 vs. 80% (109217/135293), p &amp;lt; 0.01). PR in 2021 were higher (39.2% (222 pregnancies / 567 embryo transfers) vs. 35.2% (6837/19420), OR = 1.18 [0.99-1.41] p = 0.05) while using hrFSH compared to recFSH. The effect was even stronger when comparing patients aged 30-34y (46.2% (98/212) vs. 38.6% (2967/7865), OR = 1.41 [1.07-1.88], p = 0.01). Another quantitative difference could be observed for patients aged 30-34y in their first IVF/ICSI-cycle (PR 48.5% (63/130) vs. 39.5% (1926/4873), OR = 1.44 [1.00-2.07], p = 0.05). Including all cycles between 2017-2021 resulted in higher PR for couples treated with hrFSH (38.3% (790/2062) vs. 36.2% (37439/103357), OR = 1.09 [1.00-1.20], p = 0.049). Cumulative PR including consecutive frozen embryo transfers after the first stimulation showed significantly higher PR while using hrFSH (81.6% (422/517) vs. 71.3% (17373/24367), OR = 1.79 [1.42-2.23], p &amp;lt; 0.01). Finally, cumulative LBR per ET was significantly increased if hrFSH was used for ovarian stimulation (60.0% (310/517) vs. 51.9% (12648/24367), OR = 1.39 [1.16-1.66], p &amp;lt; 0.01) compared to recFSH. Limitations, reasons for caution Since we analyzed RWD, comparison with large clinical trials should be considered carefully. PR and LBR was calculated only using stimulations which successfully generated ET. Moreover, individual AMH values are not transmitted to the German IVF Registry. Therefore, difference in ovarian reserve between study groups can’t be excluded. Wider implications of the findings In this large, prospective RWD, higher cumulative LBR and PR using hrFSH compared to recFSH, irrespective of age or infertility diagnosis, supports the use of individualized fertility treatment approach based on hrFSH. These results are consistent with previous retrospective findings. Trial registration number Not applicable

ESHRE good practice recommendations on recurrent implantation failure.

ESHRE good practice recommendations on recurrent implantation failure.

Clinical Pregnancy Is Not Associated with Sperm Quality in POSEIDON Group 1 and 2 Patients

This study is aimed at establishing the effects of varying sperm quality on IVF-ICSI/IMSI outcomes in unexpected poor ovarian responder subjects of POSEIDON groups 1 and 2. In the present study, 1,263 couples with female partners who fulfilled the POSEIDON group 1 and 2 criteria were recruited. All couples underwent ICSI or IMSI at Morula IVF Jakarta Clinic, Indonesia. Patients were subsequently classified into six groups, according to semen conditions of the respective male partners: (1) normozoospermic, (2) teratozoospermia, (3) oligoasthenoteratozoospermia (OAT), (4) asthenozoospermia, (5) severe OAT, and (6) cryptozoospermia. Laboratory and clinical outcomes of the IVF-ICSI/IMSI program were then evaluated. Early and late embryonic development parameters including the number of fertilization, cleavage and blastocyst stages, and blastocyst quality differed significantly among the different sperm quality groups ( p &lt; 0.05 ). No difference was observed in the number of embryo transfers and clinical pregnancy among the studied groups ( p &gt; 0.05 ). Our study has demonstrated the effect of sperm quality on embryo development at the early and later stages; however, the clinical pregnancy was not impaired in the unexpected poor responders of POSEIDON groups 1 and 2.

ART outcomes of patients in women with Isolated Hypogonadotropic Hypogonadism: a retrospective study in China

BackgroundIsolated Hypogonadotropic Hypogonadism (IHH) is a rare reproductive disorder caused by the dysfunction of the gonadotropin-releasing hormone axis. Patients with IHH typically fail to enter or develop through puberty and retain infertile without an exogenous hormone supplement. This study aimed to investigate the population characteristics and reproductive outcomes in IHH patients undergoing assisted reproductive technology (ART) treatment, and evaluate the best-performed predictor for ovarian response and clinical pregnancy in patients with IHH.MethodsThis retrospective cohort study included 83 women with IHH who underwent fresh ART cycles and non-diagnosed controls (n = 676). The receiver operating characteristic curves were generated to assess the predictor for the ovarian response. Logistic regression analyses were performed to investigate the independent factors for clinical pregnancy in IHH.ResultsThe basal hormone levels were significantly lower in the IHH group compared to the control group. The fertilization rate and 2PN rate were significantly higher in IHH groups, as was the number of transferable embryos. The study identified that AMH was the best predictor of high ovarian response in IHH, with an AUC of 0.767 (0.573, 0.961). Conversely, the follicle-to-oocyte index (FOI) exhibited the highest AUC of 0.814 (0.642, 0.985) for predicting low ovarian response. Based on FOI values, the IHH patients were divided into two groups, and the study found a significant increase in clinical pregnancy rate (43.8%, 58%; P < 0.001) and live birth rate (37.5%, 58%; P < 0.001) from the low FOI to the normal FOI groups. Moreover, the number of oocytes retrieved, fertilized embryos/rate, 2PN embryos/rate, and number of excellent quality embryos were significantly higher in the normal FOI group (P < 0.001 or P = 0.005) than in the low FOI group. Logistic regression analyses revealed FOI to be the independent factor affecting clinical pregnancy in IHH patients.ConclusionsThe study findings suggest that patients with IHH were good responders to IVF treatment. Although AMH was the best-performed predictor for the high ovarian response, FOI had the best capability in predicting the low ovarian response. FOI was an independent factor affecting clinical pregnancy in IHH undergoing IVF/ICSI.

Homocysteine serum levels correlate with the number of failed IVF cycles even when within normal range.

Repeated implantation failure is a common challenge in daily practice. Homocysteine and vitamin B12 have been associated with reproductive processes among patients undergoing in vitro fertilization; however, their involvement in repeated implantation failure has not been assessed. We explored possible associations of serum homocysteine and vitamin B12 with repeated implantation failure. A retrospective analysis of 127 women who underwent ≥ 3 unsuccessful embryo transfers during 2005-2016, at the Fertility and In Vitro Fertilization Unit at Carmel Medical Center. After at least 3 IVF failures serum levels of homocysteine and vitamin B12 were measured. The mean patient age was 33.5 ± 5.2years. The mean number of embryo transfers was 4.6 ± 1.5. The mean total cumulative number of embryos transferred was 10.4 ± 5.2. Mean serum levels of homocysteine were 8.6 ± 3.7µM/L, and of vitamin B12 were 302.5 ± 155.3pg/ml. Homocysteine levels were within the normal range (< 14µM/L) in 95.8% of the patients. Yet, the levels of homocysteine correlated with both the number of failed embryo transfers (r = 0.34, p = 0.004) and the total cumulative number of transferred embryos (r = 0.36, p = 0.002). Our findings suggest an association between serum homocysteine levels and the occurrence of repeated implantation failure, even when homocystein levels were within the normal range. It should be studied whether nutritional supplementation to modulate serum homocysteine levels may improve treatment outcome.

Comparing endometrial preparation methods in frozen embryo transfers – Does a previous live birth make a difference?

Research questionDoes the outcome of a medicated or natural endometrial preparation for a frozen cycle differ if a patient has previously experienced a failed fresh cycle? DesignRetrospective matched case-controlled study to investigate frozen embryo transfer (FET) outcomes in women undergone medicated or natural endometrial preparation, with adjustment to the history of previous live birth. 878 frozen cycles were included for analysis, over a period of 2 years. ResultsAfter adjusting for the number of embryos transferred, endometrial thickness and the number of previous embryo transfers, there was no difference in live birth rate (LBR) between medicated-FET and natural-FET groups regardless of the previous fertility outcome (p = 0.08). ConclusionsA previous live birth does not affect the outcome of a subsequent frozen cycle, regardless of whether medicated- or natural endometrial preparation is used.