bluuebunny/crossref_metadata_2025_split huggingface dataset:
P–162 Laser-assisted collapse of blastocysts prior to vitrification improves clinical outcomes
Authors: Ten J , Guerrero J , Rodríguez-Arnedo A , Martí L , Herreros M , Díaz N , Sellers R , Tió M C , Bernabeu A , Llácer J , Bernabeu R 
Published: August 2021

Abstract

Study question
What is the effect of artificial laser-assisted collapse before vitrification on pregnancy and implantation rates after transfer of vitrified-warmed blastocysts?

Summary answer
The artificial shrinkage by laser-induced collapse before vitrification significantly increased the implantation and clinical pregnancy rates after single thawed embryo transfer.

What is known already
Freeze all, cycle segmentation and, in general, single embryo transfer (SET) strategies (for example trophectoderm biopsy-based aneuploidy testing) have targeted blastocysts vitrification as the best option for reproductive practice worldwide. Artificial shrinkage seems to be a pre-vitrification parameter associated with an increased embryo survival after warming and implantation rate. However, the available medical evidence shows controversial results with only a limited number of prospective studies assessing the subject.

Study design, size, duration
This prospective cohort study evaluated 394 women who underwent a frozen blastocyst transfer at Instituto Bernabeu between July and December 2020. All patients were prepared with substitutive cycle and received single blastocyst embryo transfers.

Participants/materials, setting, methods
Before embryo vitrification on day 5 of development, some expanded and/or early hatching blastocysts (A/B ASEBIR categories) were artificial laser-assisted collapsed. (n = 83, study group). 311 embryos of the same quality and day of development were not collapsed (control group). We compared the embryo survival rate, clinical, implantation and miscarriage rates between groups. The statistical analysis was performed using SPSS (version 20.0).

Main results and the role of chance
The two groups were comparable in terms of maternal age (39.79 ± 3.83, control group; 40.21 ± 4.45, study group; p = 0.341). Embryo survival rate resulted in 100% in both groups.
Regarding clinical outcomes, collapsed blastocysts significantly increased the positive pregnancy test and the clinical pregnancy and implantation rate compared to the control group, respectively (positive test: 69,9% vs 43,4%, p = 0.000018, odds ratio (OR)= 3.02 [95% CI 1.80–5.08]; clinical pregnancy and implantation: 56,6% vs 35,4%, p = 0.000041, OR = 2.39 [95% CI 1.46–3.90]). The miscarriage rate was not affected by the blastocyst collapse effect (23,6% in the control group vs 27,6% in the study group, p = 0.593, OR = 1.23 [95% CI 0.57–2.68]).

Limitations, reasons for caution
This is a non-randomized controlled study. Additional RCTs are warranted to corroborate our findings.
Wider implications of the findings: Considering the large number of blastocyst vitrification cycles that are carried out worldwide, artificial laser-assisted collapse before vitrification has the potential to increase the clinical results in benefit of many patients.

Trial registration number
Not applicable
P–249 Does the re-expansion of thawed embryos affect the clinical outcomes of human blastocyst vitrification?
Authors: Huong T , Ph. Th. Tú A , Mai L H , Doã. Thảo N , Mạnh C A 
Published: August 2021

Abstract

Study question
Is that essential for prolonged culture of thawed blastocysts in order to be fully re-expanded before transferring?

Summary answer
Ongoing pregnancy rates decreased in blastocysts that not fully re-expanded after thawing. What is known already: The thaw survival of blastocysts is examined based on morphology of inner cell mass (ICM) and trophectoderm (TE). However, thawed blastocysts experience multiple changes in morphology and might be collapse after thawing due to the presence of blastocoel cavity. It is then difficult to evaluate blastocyst quality. Therefore, the blastocyst re-expansion is considered as a criteria to assess quickly the competent embryos. It also reflects the status energy metabolism from high quality embryo. After all, there are still some controversial opinions about the influence of re-expansion status after thawing.

Study design, size, duration
This was a retrospective study based on data collected between October 2019 and December 2020. A total 528 thawed blastocysts which were divided into two groups according to the post-thaw reexpansion status: fully re-expanded blastocysts (n = 416), partial or no re-expanded blastocysts (n = 112). The re-expansion status of blastocyst was assess prior to loading on the catheter by senior embryologists.

Participants/materials, setting, methods
Primary outcome is ongoing pregnancy. Only frozen single D5 transfer cycles were included. We excluded the frozen sperm/oocytes/embryos donation cycles, missing data, non-intact embryos after thawing. Statistical analyses were performed with T or chi-squared tests. Multivariable regression analysis was performed adjusting for the following confounding factors: age, BMI, embryo quality, re-expansion status, biopsied blastocyst.

Main results and the role of chance
Female age, BMI, number of previous cycles, endometrial thickness, positive HCG results, clinical pregnancy rate were comparable among patients within two groups. The rate of ongoing pregnancy rate in group 1 was significant higher compared with group 2 (51 vs 40.2, p &lt; 0.05). The number of good quality blastocyst transferred in group 1 was higher than in group 2 (p &lt; 0.001). However, under the same embryo quality, there were no difference between clinical pregnancy rate and ongoing pregnancy rate between two groups. When logistic regression were performed: only embryo quality, but not the re-expansion status, was noted to be an independent predictor of ongoing pregnancy (OR = 3.53;95% CI; 1.734–7.184;p=0.001).

Limitations, reasons for caution
The main limitation of the study is its retrospective design.
Wider implications of the findings: Clinical outcomes are comparable between re-expanded blastocyst and partial or no re-expanded blastocysts, although ongoing pregnancy can be improved when embryos are fully expanded. As expected, blastocysts quality has the most important impact on ongoing pregnancy rate.

Trial registration number
Not applicable
P–281 Is it worth to go to blastocyst when there are less than 4 embryos on day 3?
Authors: Gonzale. Marti B , Pessah C , Entezami F 
Published: August 2021

Abstract

Study question
Are pregnancy rates similar with blastocyst transfer compared to D3 transfer for patient with a poor embryo yield.

Summary answer
In poor prognosis patients, more D3 embryos are needed to result in similar outcome compared to single blastocyst and it increases the multiple pregnancy risk.

What is known already
Good prognosis patients benefit from a blastocyst transfer rather than cleavage-stage embryo because day 3 morphology has limited predictive value for subsequent developmental. A Cochrane meta-analysis in 2016 found a higher live birth rate per transfer in the blastocyst group compared to cleavage-stage and no difference in miscarriage and multiple pregnancies.
However, in unselected patients, studies have yielded conflicting results and especially in poor prognosis patients at risk of transfer cancellation.
A threshold of four good embryos on the third day has been previously correlated with blastocyst yield and live birth rate compared with cleavage-stage embryo transfer.

Study design, size, duration
We analyzed the outcome of 1115 cycles with less than 4 embryos during 2019–2020 and compared the results between two groups of D3 and D5 transfers.

Participants/materials, setting, methods
Amongst 1115 study cycles, in 691 cycles a D3 transfer was performed and in 424 cycles a D5 transfer was performed. We compared transfer cancellation rates, mean number of transferred embryos and ongoing pregnancy rates between the two groups and also in subgroups with female age &lt;37 and female age &gt;37. The statistical analyses were done by Chi square and t-test for paired samples.

Main results and the role of chance
In the overall study population, the mean female age was 36.3 ± 4.3 years, the mean number of obtained embryos was 2.4 ± 1.0, the mean number of transferred embryos was 1.4 ± 0.8. 17.2% of the cycles resulted in transfer cancellation (6.2% in D3 transfer group and 35.0% in D5 transfer group). After D3 transfer the ongoing pregnancy rate (OPR) per transfer was 21.5% compared to 39.7% in D5 transfers (p &lt; 0.05). A similar pattern was observed in subgroups of age &lt;37 years and &gt;37 years with OPR per transfer significantly higher when D5 transfer was performed. Notably more embryos were transferred on D3 compared to D5 (mean number 1.4 for D3 and 1 for D5). Nonetheless, OPR were similar per cycle in both groups and subgroups of different ages.

Limitations, reasons for caution
A prospective randomized controlled trial is needed to confirm these results that are consistent with previously reports on retrospective and observational studies.
Wider implications of the findings: In poor prognosis patients with low embryo yield, D3 and D5 transfers result in similar OPR per cycle. Transferring at blastocyst stage is not inferior to D3, despite the high cancellation rate, and appears safer permitting a single embryo transfer to avoid multiple pregnancy.

Trial registration number
Not applicable
P–354 Analysis of pregnancy and miscarriage rates in anti-centromere antibodies (ACA)-positive patients treated with ART
Authors: Kida Y , Tokoro M , Kitasaka H , Yoshimura T , Fukunaga N , Asada Y 
Published: August 2021

Abstract

Study question
Do ACA have an effect on pregnancy and miscarriage rates of human embryos?

Summary answer
The present results suggest that in ACA-positive cases, the pregnancy rate per transfer was significantly lower, although the miscarriage rate was not affected.

What is known already
We have previously shown that patients with high levels of anti-centromere antibody (ACA), (one of the anti-nuclear antibodies (ANA)), frequently have dispersal of the female chromosomes in the cytoplasm. Additionally, we reported that the clinical outcome was characterized by a low oocyte maturation rate following ovum pick up and high multiple pronuclear formation rate after fertilization. However, the post-implantation course of embryos with ACA-positive cases has not yet been reported. Therefore, in this study, we analyzed the pregnancy and miscarriage rates in ACA-positive patients treated with Assisted Reproductive Technologies (ART).

Study design, size, duration
6581 patients who underwent embryo transfer after antinuclear antibody testing between January 2014 and February 2020 were included in the analysis.

Participants/materials, setting, methods
The subjects were classified into three groups: ANA-negative (without ACA or any other ANA), ACA-positive (with only ACA) and ANA-positive (with ANA but not ACA). The cycle in which the gestational sac was confirmed was considered a positive pregnancy. The pregnancy and miscarriage rates were compared among the groups using “Ryan Test” for statistical analysis.

Main results and the role of chance
Of the 6581 eligible cases, the incidence of antinuclear antibody were 71.3% (4695/6581; ANA-negative), 0.9% (61/6581; ACA-positive) and 27.7% (1825/6581; ANA-positive). The pregnancy rates based on the total number of embryo transfer cycles for each were ANA-negative: 31.5% (5283/16792), ACA-positive: 17.6% (41/233), and ANA-positive: 32.4% (1891/5833). The pregnancy rates were significantly lower in the ACA-positive group than in the other groups. The miscarriage rate was 29.4% (1553/5283) in ANA-negative, 31.7% (13/41) in ACA-positive, and 28.0% (529/1891) in ANA-positive, with no significant difference between the three groups.

Limitations, reasons for caution
Retrospective analysis
Wider implications of the findings: ACA-positive patients may benefit from a treatment strategy to increase the absolute number of oocytes by obtained in order to increase the chances of normal fertilization and attainment of implantation.

Trial registration number
none
P–368 Dynamic metabolomic profiling during early implantation period
Authors: Zhang Y , Zhao Y W , Wang C C , Li T C 
Published: August 2021

Abstract

Study question
To investigate the different metabolomic profiling in serum between pregnant and non-pregnant women during early implantation period.

Summary answer
Metabolomics of progesterone-related hormones enhances from ET day3 for pregnancy women compared with non-pregnancy women.

What is known already
Metabolomics is based on high-throughput analytical methods to identify and quantify metabolites. Compared to other omics study, metabolomics is the closest one to the phenotype, allowing the observation of dynamic changes in phenotype at specific timepoints. So far there is no published work about the metabolomics profile in human early implantation period. Study design, size, duration: Study design: comparative study. Size: 14 pregnancy women and 14 non-pregnancy women. duration: time-course.

Participants/materials, setting, methods
Participants: pregnancy women and unpregnancy women after embryo transfer (ET). Setting: university-based study. Methods: Peripheral blood were collected at ET day0, 3, 6 and 9. metabolomic profiling in serum by platforms of capillary electrophoresis-mass spectrometry (CE-MS) and liquid chromatography–mass spectrometry (LC-MS).

Main results and the role of chance
There were no statistical difference of the age, BMI, basal FSH level, endometrium thickness on the day of embryo transfer, distribution of primary and secondary fertility, embryo transfer cycle as well as the infertile types between the two groups. After deleting those with over 50% missing data, we finally have 310 metabolites into statistical analysis. Among the 310 metabolite, lipid metabolites account the largest percentage, nearly half of all metabolites. The second biggest class of metabolites in our data was organic acids. Combined results in repeated measurement ANOVA (RM-ANOVA) and ANOVA-simultaneous component analysis (ASCA) as well as multivariate empirical Bayes time-series analysis (MEBA), we finally found that progesterone-related hormones were the most important metabolites for the whole time-series data. Those significant metabolites showed a significant down regulation from ET day0 to ET day3 and up regulation from ET day3 to ET day9.

Limitations, reasons for caution
we have limited sample size for this study and further validation is necessary for confirmation.
Wider implications of the findings: The phenomenon of upregulation of progesterone-related hormones from day3 in pregnancy group might be related to the embryo-originated hcg. Because the embryo has entered into endometrium at day3 and produced cytokines, hcg and other interaction with endometrium.

Trial registration number
NA
P–370 RPL-protease A as a potential biomarker for predicting recurrent pregnancy loss
Authors: Pei C Z , Park H B , Choi H S , Choi B , Park H Y , Jung H Y , Baek K H 
Published: August 2021

Abstract

Study question
Could the reduction of RPL-protease A be involved in the dysfunctional trophoblast for resulting in recurrent pregnancy loss (RPL).

Summary answer
Low expression of RPL-protease A may result in RPL and low serum RPL-protease A level may be a potential biomarker for predicting RPL.

What is known already
The RPL-protease A is expressed and secreted by placenta. The RPL-protease A is involved in the pathogenesis of pre-eclampsia, and the serum RPL-protease A level is higher in the patients with pre-eclampsia than that of normal groups. In our previous study, we identified that the RPL-protease A mRNA level was lower in the villi of patients with RPL than that of normal groups.

Study design, size, duration
Using the CRISPR/Cas9 system, the RPL-protease A gene knockout BeWo cell (BeWo KO) line was established, and the wild type (BeWo WT) and BeWo KO cells were applied to investigate the roles of RPL-protease A in trophoblasts. The human serum RPL-protease A levels were investigated by Western blot analysis and ELISA kit.

Participants/materials, setting, methods
The cell-cell fusion, cell counting analysis, invasion and scratch wound assays, cell cycle analysis, and immunocytochemical analysis were used to investigate cellular functions of RPL-protease A in trophoblast. The sera were obtained from 32 normal pregnant women and 60 women with RPL. The Western blot analysis and ELISA were used for detection of serum RPL-protease A levels.

Main results and the role of chance
The β-hCG was detected in fused BeWo WT cells, while the BeWo KO cells cannot fuse and did not express the β-hCG. The ability of invasion was decreased, but the capacity of migration and proliferation was higher in BeWo KO cells than BeWo WT cells. Cell fusion related factor (β-hCG), and cell invasion related factors (MMP–2 and MMP–9) were highly expressed in BeWo WT cells, and cell related factor (FAK), and cell proliferation related factors (ERK, p38, JNK, MKK3, MKK6, Raf, and Ras) were highly expressed in BeWo KO cells. The Western blot analysis and ELISA indicate that the serum RPL-protease A level was decreased in patients with RPL compared to that of normal groups.

Limitations, reasons for caution
The results of this study have the limitation of RPL-protease A functions in vitro.
Wider implications of the findings: The cellular functions of RPL-protease A in trophoblasts were investigated to explain the pathogenesis of RPL, and low serum RPL-protease A level can be used for a potential biomarker predicting RPL.

Trial registration number
Not applicable
P–392 Clinical outcomes of endometrium receptivity analysis(ERA) testing in patients with repeated IVF failures
Authors: Yang W J , Lu F , Che. yu L , Hsuan Y. Y , Chin. Hung C , Jac. Yujen H 
Published: August 2021

Abstract

Study question
Is ERA testing different between RIF patients with control group?

Summary answer
In RIF patients, there were more chances of non-receptive endometrium. ERA testing may be helpful for the patients with repeated IVF failure. What is known already: The endometrium receptivity analysis testing might have the ability to detect the implantation window. In repeat implantation failure patients, detecting of precisely implantation window may have some benefits.

Study design, size, duration
This was a single-center retrospective observational study. Two hundred and forty-nine patients who underwent ERA testing following frozen-thawed embryo transfer in our center were including in this study between January 2019 and May 2020.

Participants/materials, setting, methods
181 patients having unexplained repeated IVF failure (RIF group, at least tow implantation failure) and 68 patients having no experience with embryo transfer (Control group) who underwent ERA testing were including in this study. Both of Patients having a receptive (R) ERA and having a non-receptive (NR) ERA underwent a personalized embryo transfer (pET) on ERA. ERA results and clinical outcomes compared between RIF group and control group were analyzed by Chi-square test.

Main results and the role of chance
The proportion of R/NR results were 33:35 for the RIF group and 118:63 for the Control group, demonstrating the displacement of the window of implantation in patients with RIF. Our results revealed an endometrial factor in 51% RIF patients, which was significantly greater than the Control group 34.8% (P = 0.02). Among the patients with NR ERA result, there are not significantly difference in clinical pregnancy rate in the RIF group compared with control group (57.1%. vs. 61.9%). The clinical pregnancy rate of the patients with receptive ERA result also is comparable in both group (70.3% vs. 66.7%).

Limitations, reasons for caution
This is a retrospective, single center study with limited case number. There were may some bias with ERA testing errors.
Wider implications of the findings: In RIF patients, there were more chances of non-receptive endometrium. ERA testing may be helpful for the patients with repeated IVF failure. Larger randomized studies are required to validate these results.

Trial registration number
18MMHISO70e
P–394 Intralipid infusion at time of embryo transfer in women with history of recurrent implantation failure: a systematic review and meta-analysis
Authors: Rimmer M P , Black N , Keay S , Quenby S , Wattar B. H.A 
Published: August 2021

Abstract

Study question
What is the effectiveness of IV Intralipid (IVI) in improving pregnancy rates in women undergoing IVF with history of Recurrent implantation failure (RIF) to improve reproductive outcomes.

Summary answer
The evidence to support the use of IVI at the time of embryo transfer in women with RIF is limited. More RCTs are needed. What is known already: Optimising the implantation process following embryo transfer remains a clinical challenge with 10% of couples undergoing IVF affected by (RIF). Immunotherapy could help to optimise endometrial receptivity and increase the chances for successful conception in women with history of RIF. Intra-venous Intralipid (IVI), a fat-based emulsion of soybean oil, glycerine, phospholipids, egg, and polyunsaturated fatty acids, has been evaluated in several trials as a potential intervention to downregulate the uNK cells and macrophages as well as inhibit the pro-inflammatory mediators including T1 helper cells. Evidence synthesis is needed to evaluate the effectiveness of this intervention.

Study design, size, duration
We performed this systematic review using a prospectively registered protocol (CRD42019148517) and reported in accordance with the PRISMA guidelines. Participants/materials, setting, methods: We searched MEDLINE, EMBASE and CENTRAL for any randomised trials evaluating the use of IVI at the time of embryo transfer in women undergoing assisted conception until September 2020. We extracted data in duplicate and assessed risk of bias using the Cochrane Risk of Bias tools. We meta-analysed data using a random effect model and reported on dichotomous outcomes using risk ratio (RR) and 95% confidence interval (CI).

Main results and the role of chance
We included five randomised trials reporting on 843 women with an overall moderate risk of bias. All trials used 20% IVI solution at the time of embryo transfer compared to normal saline infusion or no intervention (routine care). The IVI group had a higher chance of clinical pregnancy (172 vs 119, RR 1.55, 95%CI 1.16–2.07, I2 44.2%) and live birth (132 vs 73, RR 1.83, 95%CI 1.42–2.35, I2 0%) post treatment compared to no intervention.

Limitations, reasons for caution
Our findings are limited by the small sample size and the variations in treatment protocols and population characteristics.
Wider implications of the findings: Our meta-analysis offers an overview on the value of IVI to help women affected by RIF. Given the limitations and the quality of included trials, adopting the use of IVI a-la-carte to couples undergoing IVF remains immature. IVI should not be offered until larger RCTs demonstrate a persistent benefit.

Trial registration number
CRD42019148517