Cytoplasmic String Between ICM and mTE Is a Positive Predictor of Clinical Pregnancy and Live Birth Outcomes in Elective Frozen-thawed Single Blastocyst Transfer Cycles: a Time-lapse Study

Abstract Background: In this study, we aim to investigate whether cytoplasmic string between inner cell mass (ICM) and mural trophectoderm (mTE) is a positive predictor of clinical pregnancy and live birth outcomes.Methods: 1,267 elective frozen-thawed single blastocyst transfer (eSBT) cycles cultured in time-lapse incubation system from January 2018 to May 2019 were involved in the study. Blastocysts were grouped according to the appearance of cytoplasmic strings between ICM and mTE cells, and identified as “Present” and “Absent” groups. In Present group, they were further categorized according to the quantity of cytoplasmic strings between ICM and mTE cells. Clinical pregnancy and live birth outcomes of blastocysts were used to evaluate the effect of cytoplasmic strings between ICM and mTE.Results: The baseline demographic and laboratory features were similar between the Present and Absent groups of cytoplasmic strings between ICM and mTE (P>0.05). According to the time-lapse analysis, cytoplasmic strings between ICM and mTE were more visible among good quality blastocysts. Furthermore, blastocysts with cytoplasmic strings showed a higher clinical pregnancy and live birth rates (P<0.05), and no significant differences were observed in abortion rate and birth weight (P>0.05).Conclusions: Although the previous conclusions of cytoplasmic strings were controversial, the present time-lapse analysis provides the evidence for the first time that cytoplasmic strings between ICM and mTE cells would be a positive predictor of clinical pregnancy and live birth outcomes in elective frozen-thawed single blastocyst transfer cycles.

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Cytoplasmic String Between ICM and mTE Is a Positive Predictor of Clinical Pregnancy and Live Birth Outcomes in Elective Frozen-thawed Single Blastocyst Transfer Cycles: A Time-lapse Study

10.21203/rs.3.rs-144098/v1 ◽

2021 ◽

Author(s):

Bingxin Ma ◽

Lei Jin ◽

Bo Huang

Keyword(s):

Birth Outcomes ◽

Live Birth ◽

Inner Cell Mass ◽

Cell Mass ◽

Time Lapse ◽

Clinical Pregnancy ◽

Blastocyst Transfer ◽

Single Blastocyst Transfer ◽

First Time ◽

Present Group

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P–147 The impact of blastocyst morphological parameters on live birth and singleton birthweight in single blastocyst transfer cycles

Human Reproduction ◽

10.1093/humrep/deab130.146 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

X Wang ◽

S Zhang ◽

G Lin

Keyword(s):

Live Birth ◽

Inner Cell Mass ◽

Care Center ◽

Tertiary Care ◽

Cell Mass ◽

Blastocyst Transfer ◽

Morphological Parameters ◽

Poor Grade ◽

Single Blastocyst Transfer ◽

The Impact

Abstract Study question Does blastocyst morphological parameters: blastocyst expansion degree(Expansion), inner cell mass (ICM), and trophectoderm (TE) grades affect live birth and singleton birthweight in single blastocyst transfer cyles? Summary answer The effects of blastocyst morphological parameters on live birth and singleton birthweight are different between biopsied blastocysts cycles and non-biopsied blastocysts cycles. What is known already It has been known that blastocysts with highest scores for three blastocyst morphological parameters achieve highest pregnancy rates, however, very few studies have comparatively analysed the effect of individual parameters on live birth and singleton birthweight about single blastocyst transfer cycles. Study design, size, duration This retrospective study involved all single blastocyst transfers cycles and their live birth outcome and singleton birthweight during the period from January 2014 to August 2019 at a tertiary care center. Participants/materials, setting, methods A total of 28515 single blastocyst transfer cycles were available for analysis and were divided into four groups: biopsied blastocysts cycles (BBC), thawed blastocysts cycles(TBC), blastocysts from thawed cleavage embryos cycles(BTCEC) and fresh blastocysts cycles(FBC). The primary outcome were live birth and singleton birthweight. Multiple logistics regression and linear regression analyses were respectively performed to investigate the effect of blastocyst morphological parameters on live birth and birthweight after adjusting potential confounders. Main results and the role of chance While analyzing the effect on live birth, we found that live birth of grade B ICM were lower than grade A ICM , live birth of grade C TE were lower than grade A TE and Expansion doesn’t matter. Those result were same in three kinds of non-biopsied cycles. While all three parameters were statistically independently significant in biopsied blastocysts cycles. While analyzing the effect on singleton birthweight, only Expansion was found to be statistically significant in biopsied blastocysts cycles, and birthweight of Expansion grade 5 was lower than Expansion grade 6(P = 0.005),with a mean difference of 57g(3375.12±527.91 versus 3318.42±510.33). Limitations, reasons for caution: Most blastocysts with poor grade, especially ICM grade C, were not transferred, then the effect of poor grade such as ICM grade C were still unknown. Wider implications of the findings: The study identified the association between blastocyst morphological parameters and live rate and compared the relative importance of three parameters in different kind of cycles through large size comparative analysis, which would help selecting high-quality embryos for transfer. Trial registration number Not applicable

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P–266 Morphometric assessment of Ratio of inner-cell-mass diameter to blastocyst diameter is an effective criterion to select best embryo for successful outcomes in single blastocyst transfer-cycles

Human Reproduction ◽

10.1093/humrep/deab130.265 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

N M Chimote ◽

B Chimote

Keyword(s):

Live Birth ◽

Inner Cell Mass ◽

Cell Mass ◽

Diameter Ratio ◽

Blastocyst Transfer ◽

Cutoff Value ◽

Photographic Images ◽

Live Birth Rates ◽

Single Blastocyst Transfer ◽

Inner Diameter

Abstract Study question Can semi-quantitative measurement of ICM diameter vis-à-vis blastocyst diameter, calculated from photographic images, be a significant predictor of implantation potential in single blastocyst transfer cycles? Summary answer A simple, non-invasive measurement of ICM:Blastocyst diameter ratio is a potentially effective predictor of high developmental potential, implantation, live-birth rates in single blastocyst transfer cycles. What is known already: Correlationship between quantitative measurements of blastocyst morphology such as size and shape of ICM and its implantation potential were first reported by Richter et al. Widely used Gardner and Schoolcraft’s qualitative scoring assessment is based on three major variables: expansion stage of blastocyst, cohesiveness of the inner cell mass (ICM), and consistency of trophectodermal (TE) cells. A top quality single blastocyst transfer yields implantation rate nearing 70% and live-birth rate about 50%. If an additional morphological but vital parameter evaluating ICM:Blastocyst diameter ratio is introduced to the Gardner’s blastocyst gradation system, it may help enhance IVF success rates still further. Study design, size, duration A prospective observational cohort study of women (n = 244) undergoing IVF treatment at our private fertility clinic from April 2018 until March 2020. Women with their autologous fertilized oocytes undergoing extended culture and transfer of a single fresh, at least fully expanded (Grade 3) blastocyst with a measurable ICM diameter and blastocyst inner diameter on day 5/6, irrespective of age, cycle number and indication for treatment, were included. Cryopreservation cycles were excluded. Participants/materials, setting, methods Each blastocyst was evaluated for expansion grade, ICM and TE according to Gardner et al. conventional method. Additionally, ratio of ICM diameter w.r.t. blastocyst inner diameter was also calculated from the photographic images on screen using the Hamilton-Thorne software package embedded with their laser system. Measurements were done on blastocysts where expansion had occurred between 114 and 120 hours after insemination. Implantation rates and live-birth rates were the major end-points. Main results and the role of chance A total of 244 blastocyst transfers were performed in same number of women, and 130 clinical pregnancies were achieved (53.3%). The average age of the women was 32.5 ± 4.2 years. The blastocysts that implanted successfully had an average ICM:blastocyst diameter ratio of 0. 469±0.082), whereas blastocysts that did not implant had a significantly lower ratio of 0.325±0.09 (P <.0001). No statistical significant difference was found in the TE grade between the blastocysts that implanted successfully and those that did not. Out of the 130 pregnancies achieved, 89 (68%) resulted in the delivery of a healthy baby. After ROC analysis, a cutoff value for the ICM/blastocyst ratio showed equal rank for sensitivity (0.81) and specificity (0.72). The resultant positive predictive value was 78%, and the negative predictive value was 74%. In our study, the conditional probability of achieving pregnancy upon transfer of a single blastocyst with an ICM:blastocyst ratio higher than the cutoff value of 0.4255 was 76%. This was significantly higher than the probability of pregnancy from blastocysts graded by conventional morphometry. Limitations, reasons for caution Our study is limited by the small sample size. Hence more multicentric studies are warranted to observe similar conclusion. Wider implications of the findings: The strengths of the study are the performance of single blastocyst transfers and using live births as the measurement endpoint. It is important to mention that embryo grading is inevitably subject to intra- and interobserver variations. However, with simple measurements of image data recording eliminates a degree of these variations. Trial registration number Not applicable

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P–263 Life Whisperer™, an AI-based algorithm to select non invasively best quality blastocysts for transfer: A multicenter analysis

Human Reproduction ◽

10.1093/humrep/deab130.262 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

P Muño. Espert ◽

Y Galiana ◽

L Medrano ◽

J Ballester ◽

L Ortega ◽

...

Keyword(s):

Roc Curve ◽

Inner Cell Mass ◽

Cell Mass ◽

High Sensitivity ◽

Roc Curves ◽

Time Lapse ◽

Clinical Pregnancy ◽

Embryo Selection ◽

Computer Assisted ◽

Stage Duration

Abstract Study question Is the AI-based Life Whisperer™ (LW) tool, suitable to evaluate blastocysts quality and predict clinical pregnancy (CP) in couples undergoing ICSI cycles? Summary answer LW blastocyst score is comparable to the scores of other classification methods. This AI model showed high sensitivity and a comparable specificity for CP. What is known already The morphology grading is the most widely used method for the selection and classification of the embryos in clinical practice.However,this evaluation entails intervariability and intravariability decision among the embryologists.Recently, research has been focused on new embryo selection systems based on computer-assisted evaluation such as time-lapse with complex algorithms that allow the recognition of objective parameters of the embryo morphology.The implementation of these technologies requires substantial investments that are not available for all clinics.LW is a new embryo selection method based on AI,where specific hardware is not needed,as it is based on single blastocyst images taken with a routine microscope. Study design, size, duration Between 2017–2020, a total of 513 Day–5 blastocysts, after ICSI, comming from egg donation treatment were included in this retrospective-multicentre study.Day–5 embryos were evaluated with 3 classification methods:Gardner’s blastocyst grade (GB), the computer derived-output Eeva (EV) and LW AI-supported system. The good quality blastocysts were first evaluated using the GB and EV scores and subsequently compared with the LW scores.The sensitivity and specificity of LW was assessed to validate this system as a clinical pregnancy predictor. Participants/materials, setting, methods A total of 513 Day–5 blastocysts, from 134 oocyte donation cycles, were evaluated first by GB score: expansion (1–6), inner cell mass and throphoectoderm (A-C).EV analyses the cell division timing P2 (2cells stage duration) and P3 (3cells stage duration) differentiating three categories:High,Medium and Low(VerMilyea et al.,2014).LW scores ranked 1–10 from a single Day–5 blastocyst HR Image performed on inverted microscope,with a threshold >5 for defining a viable blastocyst.T-test and ROC-curves were used for statistical analysis. Main results and the role of chance The average of LW score obtained from GB higher blastocyst expansion score (≥4) was 7.48±0.09, while the average of LW score obtained from GB lower blastocyst expansion score (<4) was 4.69±0.3 (P < 0.001). The average of LW score yielded from GB good morphology of Inner Cell Mass and trophoectoderm (AA,AB,BA) was 7.98±0.1 while the average of LW score obtained from GB lower quality blastocyst score (BB,BC,CB,CA,AC) was 6.36±0.156 (P < 0.001).The average of LW score resulted from EV High blastocysts was 7.42±0.17, while the average of this obtained from EV low score was 6.43±0.3 (P = 0.009).A correlation between EV and LW score could be assesed, except for the blastocyst that are considered Medium score from EV. Therefore, a strong correlation between GB and LW system, as well GB+EV and LW, was found and an equivalent usability of the LW tool could be confirmed. The analyse of LW score for transferred embryos (N = 156), using ROC curve, showed a high sensitivity (0,928) but a low specificity (0,154) with a threshold of 5. Regarding our data, ROC curve shows that a threshold of 8,46 could enhance the prediction of CPR because in this point the specifity value is higher than 0.5. Limitations, reasons for caution The LW score validation compared to GB and EV methodology was carried out on a small number of embryos.Additionally,not all embryos had been transferred at the time of the analysis.Thus to enhance the accuracy of these data and the specificity of the clinical prediction, a higher sample size is needed. Wider implications of the findings: Blastocyst selection looks equivalent between all systems,but the LW tool is more objective and faster, saving time and costs significantly, without needing substantial hardware investments. Additionally,the LW-system shows almost the highest sensibility and may also improve the specificity by self-learning feeding the AI-system, thus tailoring predictions to each laboratory unique environment. Trial registration number NA

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Can the location of a trophectoderm biopsy contribute to human blastocyst development ?

10.1101/109298 ◽

2017 ◽

Author(s):

Tomoe Takano ◽

Miyako Funabiki ◽

Sagiri Taguchi ◽

Fumie Saji ◽

Namiko Amano ◽

...

Keyword(s):

Clinical Outcomes ◽

Clinical Evidence ◽

Inner Cell Mass ◽

Cell Mass ◽

Multivariate Logistic Regression Analysis ◽

Blastocyst Transfer ◽

Trophectoderm Biopsy ◽

Blastocyst Development ◽

Human Blastocyst ◽

Single Blastocyst Transfer

AbstractThe influence of the location of a trophectoderm biopsy in human blastocysts on the development of those blastocysts has not yet been investigated. In our prospective study (n=92), our multivariate logistic regression analysis indicated that blastocoel development was influenced by the location of the trophectoderm biopsy (p=0.049) and by the type of human blastocyst used (fresh or thawed) (p=0.037), regardless of the patient’s age (p=0.507) and the number of days for the human blastocyst in the pretrophectoderm biopsy (p=0.239). Therefore, when a trophectoderm biopsy is close to the inner cell mass (ICM) in human blastocysts, it improves the progress of blastocoel development.Clinical evidence suggests that the progress of blastocoel development is a predictor of clinical outcomes after single blastocyst transfer. Therefore, when the trophectoderm biopsy is done from near the ICM, improvement of clinical outcomes after single blastocyst transfer may be expected.

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Transfer of hatched blastocyst can result in skewed sex ratio: a retrospective cohort study

10.21203/rs.3.rs-1011865/v1 ◽

2021 ◽

Author(s):

Jinliang Zhu ◽

Ying Lian ◽

Xinjie Zhuang ◽

Shengli Lin ◽

Xiaoying Zheng ◽

...

Keyword(s):

Sex Ratio ◽

Inner Cell Mass ◽

Cell Mass ◽

Poor Quality ◽

Blastocyst Stage ◽

Neonatal Outcomes ◽

Blastocyst Transfer ◽

Female Ratio ◽

Single Blastocyst Transfer ◽

Blastocyst Quality

Abstract Background The correlation between blastocyst quality and birthweight, neonatal outcomes is still controversial. There is a significantly higher male: female ratio among good quality blastocysts (advanced trophoderm morphology) but in the expansion degree, the significance for sex ratio is unclear. Methods A total of 617 and 6803 live singleton births resulting from the transfer of fresh and frozen-thawed single blastocysts in the Reproductive Medicine Center of Peking University Third Hospital from 2009 to 2020 were included. Live singleton births from fresh and frozen-thawed single blastocyst transfer were stratified by inner cell mass/trophoderm morphology and degree of blastocoel expansion. Multivariate linear regression was used to analyze the correlation between expansion, inner cell mass/trophoderm morphology, and birthweight, Z score, gestational weeks. Logistic regression was used to analyze the relationship between expansion, ICM/TE morphology and sex, neonatal outcomes. Results There was no significant correlation between birthweight, neonatal outcomes and blastocyst quality in fresh and frozen-thawed single blastocyst transfer cycles. However, the proportion of male infants in the hatched blastocyst (stage-6) group (67.9% vs. 54.2%; p < 0.001) [OR: 1.76 95% CI (1.34–2.32)] and hatching blastocyst (stage-5) group (61.7% vs. 54.2%; p = 0.001) [OR: 1.36 95 C.I (1.14ཞ1.62)] was significantly higher than that in the expanded blastocyst (stage-4) group. Conclusions The transfer of poor-quality blastocysts is unlikely to affect birthweight and neonatal health; however, transfer of stage-6 blastocysts can result in extremely skewed sex ratio.

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The Morphology of Inner Cell Mass Is the Strongest Predictor of Live Birth After a Frozen-Thawed Single Embryo Transfer

Frontiers in Endocrinology ◽

10.3389/fendo.2021.621221 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jihui Ai ◽

Lei Jin ◽

Yu Zheng ◽

Peiwen Yang ◽

Bo Huang ◽

...

Keyword(s):

Embryo Transfer ◽

Live Birth ◽

Pregnancy Outcomes ◽

Birth Rate ◽

Inner Cell Mass ◽

Cell Mass ◽

Live Birth Rate ◽

Single Embryo Transfer ◽

Clinical Pregnancy ◽

Stage 4

BackgroundThe scoring system for human blastocysts is traditionally based on morphology; however, there are controversies on the effect of morphology parameters on pregnancy outcomes. The aim of this study is to evaluate the predicting value of each morphology parameter on pregnancy outcomes in a setting of single embryo transfer.MethodsThis is a retrospective cohort study on patients undergoing frozen-thawed single blastocyst transfer at our center, between Jan. 2009 and Dec. 2018. A total of 10,482 cycles were analyzed. The blastocysts were scored according to the expansion and hatching status, morphology of inner cell mass (ICM), and cells of trophectoderm (TE). The primary outcome measure was live birth rate. One-way analysis of variance, chi-square test, and multiple logistic regression were used for statistical analysis.ResultsThe clinical pregnancy rate was lower in the blastocysts of stage 3 (48.15%), compared with those of stage 4 (56.15%), stage 5 (54.91%), and stage 6 (53.37%). The live birth rate was lower in the blastocysts of stage 3 (37.07%), compared with those of stage 4 (44.21%) and stage 5 (41.67%). The rates of clinical pregnancy (A: 66.60%, B: 53.25%, C: 39.33%) and live birth (A: 54.62%, B: 41.29%, C: 28.45%) were both decreased with decreasing grade of ICM morphology, and these differences were pairwise significant. The miscarriage rate of blastocysts with ICM grade A was lower, compared with ICM grade C (17.53 vs. 27.66%). Blastocysts with TE morphology of C had lower rates of clinical pregnancy (43.53%) and live birth (32.57%), compared with those with TE morphology of A and B (clinical pregnancy rate: 64.26% for A, 58.11% for B; live birth rate: 52.74% for A, 45.64% for B). There were no significant differences in rates of clinical pregnancy, live birth, and miscarriage between the blastocysts with TE grade A and B.ConclusionsThe blastocyst expansion stage, ICM grade, and TE grade are all associated with pregnancy outcomes. ICM grade is the strongest predictor of live birth. A blastocyst with stage 4–5, ICM grade A, and TE grade A/B should be given priority for single embryo transfer.

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