Single Vitrified-warmed Blastocyst Transfer Research Articles

Obstetrical and neonatal outcomesafter vitrified-warmed blastocyst transfer in day 1 rescue intracytoplasmic sperm injection cycles: a retrospective cohort study.

Fertilization failure often occurs in conventional IVF cycles, and day 1 rescue ICSI is frequently recommended. In this study, the effect of rescue ICSI on obstetrical and neonatal outcomes after a single blastocyst transfer in vitrified-warmed cyclesis evaluated. This cohort study was a retrospective analysis of 703 vitrified-warmed single blastocyst transfers and 219 singletons in the r-ICSI group compared with 11,611 vitrified-warmed single blastocyst transfers in the IVF/ICSI and 4472 singletons in the IVF/ICSI group, respectively, and patients just undergoing their first IVF treatments were included in this study. Pregnancy rate (PR), live birth rate (LBR), and singleton birthweight were the primary outcome measures. Multiple linear regression analysis and logistic regression analysis were performed to evaluate the possible relationship between obstetrical and neonatal outcomes and fertilization method (including IVF, ICSI, and r-ICSI) after adjusting for other potential confounding factors. PR and the LBR were lower in the r-ICSI group compared with the IVF/ ICSI group. Singletons from the r-ICSI group had a higher Z-score and the proportion of large for gestational age (LGA) newborns was greater compared with singletons from the IVF/ICSI group. The results of the study indicated that a 31% LBR after r-ICSI is acceptable for vitrified-warmed blastocyst transfer, but the safety of transfer is a concern because of the lower PR and LBR compared with IVF/ICSI. The safety of r-ICSI newborns is also a concern because of the significantly higher birthweight and the proportion of LGA in r-ICSI group newborns compared with the IVF/ICSI group.

Fatty acid supplementation during warming improves pregnancy outcomes after frozen blastocyst transfers: a propensity score-matched study

This study aimed to examine the viability of human blastocysts after warming with fatty acids (FAs) using an in vitro outgrowth model and to assess pregnancy outcomes after a single vitrified-warmed blastocyst transfer (SVBT). For the experimental study, we used 446 discarded vitrified human blastocysts donated for research purposes by consenting couples. The blastocysts were warmed using FA‐supplemented (FA group) or non-FA-supplemented (control group) solutions. The outgrowth area was significantly larger in the FA group (P = 0.0428), despite comparable blastocyst adhesion rates between the groups. Furthermore, the incidence of outgrowth degeneration was significantly lower in the FA group than in the control group (P = 0.0158). For the clinical study, we retrospectively analyzed the treatment records of women who underwent SVBT in natural cycles between January and August 2022. Multiple covariates that affected the outcomes were used for propensity score matching as follows: 1342 patients in the FA group were matched to 2316 patients in the control group. Pregnancy outcomes were compared between the groups. The rates of implantation, clinical pregnancy, and ongoing pregnancy significantly increased in the FA group after SVBTs (P = 0.0091–0.0266). These results indicate that warming solutions supplemented with FAs improve blastocyst outgrowth and pregnancy outcomes after SVBTs.

Should we should consider day 3 blastomere number during single vitrified-warmed blastocyst transfer cycle? A retrospective study

The present study investigated whether day 3 blastomere number has an effect on the clinical outcomes during single vitrified-warmed blastocyst transfer cycles. A total of 3294 vitrified-warmed single day 5 blastocyst transferred cycles were analyzed in this retrospective study from January 2018 to December 2021. The cycles were divided into ≥ 7 and < 7 blastomere groups depending on the day 3 embryo blastomere number. The clinical outcomes were compared between the two groups, moreover multivariate logistic regression analysis was conducted to investigate the correlation between the number of day 3 blastomeres and clinical outcomes. The chi-square test demonstrated that the rates of clinical pregnancy and live birth were significantly higher in the ≥ 7 blastomere group compared to the < 7 blastomere group with respect to single high-quality blastocyst transfer cycles. Conversely, these rates were similar in the two groups with respect to single low-quality blastocyst transfer cycles. These results were confirmed by multivariate logistic regression analysis. However, the miscarriage rate was higher in the < 7 blastomere group than in ≥ 7 group during low-quality blastocyst transfer cycles. These results suggested that day 3 blastomere number should be considered during single vitrified-warmed blastocyst transfer cycles. Thus, blastocsyts derived from ≥ 7 blastomere embryos are preferred when choosing the same quality blastocysts.

Human metaphase II oocytes with narrow perivitelline space have poor fertilization, developmental, and pregnancy potentials.

To analyze the fertilization, developmental, and pregnancy potentials in oocytes with narrow perivitelline space. Perivitelline space (PVS) of oocytes was evaluated at the time of ICSI, and those without sufficient PVS were judged as oocytes with narrow PVS (NPVS oocytes), and those with sufficient PVS formation were judged as oocytes with non-narrow PVS (non-NPVS oocytes). The analysis included 634 NPVS oocytes from 278 cycles and 12,121 non-NPVS oocytes from 1698 cycles. The fertilization and developmental potentials of NPVS and non-NPVS oocytes were compared by calculating odds ratios using a mixed-effects logistic regression model. We also compared the embryo transfer outcomes of those used for single vitrified-warmed blastocyst transfer after developing into the blastocyst stage. NPVS oocytes had higher odds ratios for degeneration (adjusted odds ratio [aOR], 1.555; 95% confidence interval [CI], 1.096-2.206; p = 0.0133) and 0PN (aOR, 1.387; 95% CI, 1.083-1.775; p = 0.0095), resulting in a lower 2PN rate (aOR, 0.761; 95% CI, 0.623-0.929; p = 0.0072). Even embryos with confirmed 2PN had lower odds ratios for cleavage (aOR, 0.501; 95% CI, 0.294-0.853; p = 0.0109) and blastocyst development (Gardner criteria; CC-AA) rates (aOR, 0.612; 95% CI, 0.476-0.788; p = 0.0001). Blastocysts developed from NPVS oocytes had significantly lower odds ratios for clinical pregnancy (aOR, 0.435; 95% CI, 0.222-0.854; p = 0.0156) than those developed from non-NPVS oocytes. Oocytes with NPVS have low fertilization and developmental potential, as well as low likelihood of pregnancy.

Developing and validating a prediction model of live birth following single vitrified–warmed blastocyst transfer

Research questionCan the developed clinical prediction model offer an accurate estimate of the likelihood of live birth, involving blastocyst morphology and vitrification day after single vitrified–warmed blastocyst transfer (SVBT), and therefore assist clinicians and patients? Study designRetrospective cohort study conducted at a Spanish university-based reproductive medicine unit (2017–2021) including consecutive vitrified–warmed blastocysts from IVF cycles. A multivariable logistic regression incorporated key live birth predictors: vitrification day, embryo score, embryo ploidy status and clinically relevant variables, i.e. maternal age. ResultsThe training set involved 1653 SVBT cycles carried out between 2017 and 2020; 592 SVBT cycles from 2021 constituted the external validation dataset. The model revealed that female age and embryo characteristics, including overall quality and blastulation day, is linked to live birth rate in SVBT cycles. Stratification by vitrification day and quality (from day-5A to day-6 C blastocysts) applied to genetically tested and untested embryos. The model's area under the curve was 0.66 (95% CI 0.64 to 0.69) during development and 0.65 (95% CI 0.61 to 0.70) in validation, denoting moderate discrimination. Calibration plots showed strong agreement between predicted and observed probabilities. ConclusionBy incorporating essential predictors such as vitrification day, embryo morphology grade, age and preimplantation genetic testing for aneuploidy usage, this predictive model offers valuable guidance to clinicians and patients, enabling accurate forecasts of live birth rates for any given vitrified blastocyst within SVBT cycles. Additionally, it serves as a potentially indispensable laboratory tool, aiding in selecting the most promising blastocysts for optimal outcomes.

Prioritized single vitrified blastocyst to be warmed between grades 3 or 4 blastocyst on day 5 transfer cycles.

Selecting the optimal blastocyst to implant during cryopreservation and warming is critial for in vitro fertilization success. Therefore, the aim of this study was to explore which blastocyst should be prioritized to be thawed when facing a single vitrified blastocyst on day 5 transfer. A retrospective study including 1,976 single vitrified-warmed blastocyst transfer cycles was conducted from January 2016 to December 2020. We found that grade 4 vitrified blastocyst had a higher clinical pregnancy (60.64% vs. 49.48%, P < 0.001) and live birth rates (50.12% vs 39.59%, P < 0.001) than the grade 3 vitrified blastocyst. However, no statistical difference was found between groups in miscarriage rate, birth weight, or gestational age. Besides, the grade 4 vitrified-thawed blastocyst had significant potential to develop into grade 6 blastocyst after further culturing for 16 h (73.68% vs. 48.60%, P < 0.001). The grade 6 transferred blastocyst was markedly higher in both clinical pregnancy rate (61.88% vs. 51.53%, P < 0.001) and live birth rate (50.91% vs. 40.46%, P < 0.001) compared to grade 5 transferred blastocyst. Grade 4 vitrified blastocyst is recommended when facing single vitrified blastocyst on day 5 transfer. More importantly, the "embryonic escape hypothesis" was firstly proposed to reveal the findings.

Clinical and neonatal outcomes of complete zona pellucida removal by laser-assisted hatching after single vitrified-warmed blastocyst transfer.

Laser-assisted hatching (LAH) is a widely used and unavoidable technique in assisted reproductive technology after frozen embryo transfer (FET). We aimed to investigate the safety and efficacy of completely ZP (zona pellucida) removed by an assisted laser group compared to an intact group after FET. This retrospective study involved 320 SVBT single vitrified-warmed blastocyst transfers of 213 patients who underwent clomiphene citrate (CC) based minimal stimulation protocol. This study compared 160 SVBT with ZP that were completely removed using laser-assisted (laser beams of 10-15, a wavelength of 1.48μm, and duration of 1.8-2.2ms) to 160 cases of intact SVBT. Fisher's exact test, chi-squared test, and logistic regression are used for statistical analysis. The women's age, cause of infertility, BMI, transferred embryo day, insemination methods, and blastocyst grade were not significantly different between two groups. The implantation rate (66.2% vs. 51.2%, P < 0.01), the clinical pregnancy rate (CPR, 52.5% vs. 39.3%, P = 0.01), and the live birth rate (LBR, 43.7% vs. 29.3%, P < 0.01) were significantly higher in the completely ZP removed than the intact group. In logistic regression analysis, the laser-assisted hatching group showed about 2 times higher implantation rate and CPR and LBR than the control group. But miscarriage, gestational weeks, gender, birth weight, and twin births were insignificant between two groups. Our study suggests ZP free embryo transfer by assisted laser is more effective and safer than intact embryo transfer.

Spontaneously hatching human blastocyst is associated with high development potential and live birth rate in vitrified-warmed single blastocyst transfer: A retrospective cohort study.

To investigate the effect of hatching status on predicting pregnancy outcomes in single vitrified-warmed blastocyst transfer (SVBT) by objectively subdividing pre-implantation blastocysts according to hatching status. This retrospective study included 817 SVBT cycles performed between January 2016 and December 2017. Transferred embryos were categorized according to their hatching status as follows: group I (n = 147), non-hatching blastocysts; group II (n = 484), hatching blastocysts; and group III (n = 186), completely hatched blastocysts. Hatching blastocysts (group II) were then classified based on the ratio of the blastocystic diameter outside and inside the zona pellucida into early (n = 185), mid- (n = 103), and late (n = 196) hatching stages. Implantation rate (IR), clinical pregnancy rate (CPR), live birth rate (LBR), multiple pregnancy rate (MPR), miscarriage rate, and neonatal outcomes were evaluated. For groups I, II, and III, respectively, the results were as follows: IR (28.6%, 43.6%, and 53.8%; P < 0.001), CPR (27.9%, 42.8%, and 53.2%; P < 0.001), and LBR (23.1%, 32.0%, and 42.5%; P < 0.001). Group III had better IR, CPR, and LBR. Among hatching blastocysts, late-hatching blastocysts had the highest IR (33.5%, 46.6%, and 51.5% for early, mid-, and late hatching, respectively; P = 0.002) and CPR (33.0%, 45.6%, and 50.5%; P = 0.002), with a tendency for a higher rate of LBR. Neonatal outcomes were not influenced by the hatching status. Advanced hatching status is positively associated with a higher rate of clinical pregnancy and live birth with no negative effects on neonatal outcomes. Additionally, the quantitative classification of hatching status was found to be predictive of pregnancy outcomes.

Improved pregnancy prediction performance in an updated deep-learning embryo selection model: a retrospective independent validation study

Research questionWhat is the effect of increasing training data on the performance of ongoing pregnancy prediction after single vitrified–warmed blastocyst transfer (SVBT) in a deep-learning model? DesignA total of 3960 SVBT cycles were retrospectively analysed. Embryos were stratified according to the Society for Assisted Reproductive Technology age groups. Embryos were scored by deep-learning models iDAScore v1.0 (IDA-V1) and iDAScore v2.0 (IDA-V2) (15% more training data than v1.0) and by Gardner grading. The discriminative performance of the pregnancy prediction for each embryo scoring model was compared using the area under the curve (AUC) of the receiver operating characteristic curve for each maternal age group. ResultsThe AUC of iDA-V2, iDA-V1 and Gardener grading in all cohort were 0.736, 0.720 and 0.702, respectively. iDA-V2 was significantly higher than iDA-V1 and Gardener grading (P < 0.0001). Group > 35 years (n = 757): the AUC of iDA-V2 was significantly higher than Gardener grading (0.718 versus 0.694, P = 0.015); group aged 35–37 years (n = 821), the AUC of iDA-V2 was significantly higher than iDA-V1 (0.712 versus 0.696, P = 0.035); group aged 41–42 years (n = 715, the AUC of iDA-V2 was significantly higher than Gardener grading (0.745 versus 0.696, P = 0.007); group > 42 years (n = 660) and group aged 38–40 years (n = 1007), no significant differences were found between the groups. ConclusionThe performance of deep learning models for pregnancy prediction will be improved by increasing the size of the training data.

P-139 Comparison of clinical outcomes between two hyaluronan-rich transfer medium

Abstract Study question Is there any difference in effect on clinical outcomes after single vitrified-warmed blastocyst transfer on day 5 using two hyaluronan-rich transfer medium? Summary answer There was no significant difference in rates of clinical pregnancy, implantation and miscarriage between two hyaluronan-rich transfer medium. What is known already Hyaluronan is one of the glycosaminoglycan that is naturally present in female reproductive organs and promotes the endometrial stroma and preimplantation embryo adhesion through CD44 glycoprotein receptors. Several studies demonstrated that use of hyaluronan-enriched transfer medium in women receiving either cleavage-stage or blastocyst-stage embryo improved clinical outcomes compared to the standard medium. However, studies on clinical outcomes according to two transfer medium containing different concentrations of hyaluronan are still insufficient. Study design, size, duration A retrospective study of 1047 vitrified-warmed blastocyst transfer cycles with normal responders (aged 23-35 years) was conducted from September 2018 to November 2022. All cycles with single vitrified-warmed blastocyst transfer on day 5 were evaluated. Only first IVF attempts cycles were included. All women had undergone a GnRH antagonist protocol. Cycles were divided into two groups: Group A (n = 511, EmbryoGlue®, Vitrolife) and Group B (n = 536, UTMTM, Origio). Participants/materials, setting, methods All blastocyst were graded using Gardner and Schoolcraft’s criteria. The vitrified-warmed blastocysts were equilibrated for an average of 47 minutes in two transfers medium until transfer. All blasotcyst were then loaded into an embryo transfer catheter (COOK® medical). The rates of clinical pregnancy, implantation and miscarriage were compared between the two groups. Statistical analyses were conducted using Chi-square test and Independent t-test using SPSS. Main results and the role of chance There were no significant differences in mean female age (31.6 ± 2.5 vs. 31.8 ± 2.3, P = 0.432), mean endometrial thickness (10.4 ± 1.4 vs. 10.3 ± 1.3, P = 0.478), mean oocytes retrieved (20.8 ± 6.8 vs. 20.5 ± 6.9, P = 0.470) and number of transferred good-quality blastocyst stage rate (≥BB grade, 74.8% vs. 72.6%, P = 0.423) between the two groups. We also observed similar rates of biochemical pregnancy (79.5% vs. 78.0%, P = 0.562), clinical pregnancy (71.4% vs. 69.2%, P = 0.434), implantation (72.4% vs. 70.3%, P = 0.459), ongoing pregnancy (67.5% vs. 66.2%, P = 0.659), miscarriage (5.5% vs. 4.3%, P = 0.463) and multiple pregnancy (1.4% vs. 1.6%, P = 0.782) in Group A and B, respectively. Limitations, reasons for caution This study is limited by its retrospective nature in single-center and absence of live birth information. We investigated only single vitrified-warmed blastocyst on day 5 to have data reliability. Therefore, further studies are needed to evaluate our data with vitrified-warmed blastocyst transfer on day 6 or day 7. Wider implications of the findings The present data showed that clinical outcomes were similar between two transfer medium containing different concentrations of hyaluronan. Our findings could have significant clinical implication for selection of the appropriate commercial embryo transfer medium according to IVF laboratory conditions. Trial registration number not applicable

P-113 The performance of pregnancy prediction is improved in an updated deep-learning based embryo selection model: A retrospective validation study using 3960 single blastocyst transfer cycles

Abstract Study question Does increasing the size of a training dataset improve the performance of pregnancy (fetal heartbeat) prediction in a deep-learning model? Summary answer Yes. Increasing the training data for a deep-learning model for embryo selection improved prediction of the likelihood of implantation after single vitrified-warmed blastocyst transfer (SVBT). What is known already Recently, artificial intelligence (AI) for implantation prediction after blastocyst transfer has been extensively studied. AI can address the issue of subjective assessment for the selection of blastocyst transfer. Generally, the performance of deep learning models is said to improve by increasing the training dataset. However, to the best of our knowledge, there exists no study on the effect of increasing training data on the performance of pregnancy prediction on the same deep-learning model. Study design, size, duration A total of 3,960 SVBT cycles (1 patient,1 cycle) were retrospectively analyzed. Embryos were stratified according to SART age groups. The quality and scoring of embryos were assessed by iDAScore v1.0 (iDAV1; Vitrolife, Sweden), v2.0 (iDAV2; Vitrolife, Sweden), and Gardner grading. The discriminative performance of the pregnancy prediction for each embryo scoring model was compared using the area under the curve (AUC) of the receiver operating characteristic curve for each maternal age group. Participants/materials, setting, methods Embryos were cultured in the EmbryoScope+ and/or EmbryoScope Flex (Vitrolife). iDAV2 and iDAV1 were based on an identical deep-learning architecture, but the training data for iDAV2 has been increased with 15% more data. ICM and TE were annotated according to the Gardner grading system. The degree of blastocyst expansion was Grade 4 due to our freezing policy. Furthermore, Gardner's grading (GG) was stratified into four grades (A: AA, B: AB BA, C: BB, D: others). Main results and the role of chance The AUCs of the &amp;lt; 35 years age group (n = 757) for pregnancy prediction were 0.718 for iDAV1, 0.733 for iDAV2, and 0.694 for GG. The AUC of iDAV2 was significantly higher compared to GG (P &amp;lt; 0.05). For the 35–37 years age group (n = 821) the AUCs were 0.696, 0.712, and 0.695 for iDAV1, iDAV2, and GS, respectively, and were significantly different between iDAV1 and iDAV2 (P &amp;lt; 0.05). The AUCs of the 38–40 years age group (n = 1,007) were 0.698 for iDASV1, 0.706 for iDAV2, and 0.700 for GG and there was no significant difference. The AUCs of the 41–42 years age group (n = 715) were 0.734, 0.745, and 0.696 for iDAV1, iDAV2, and GS, respectively, and the AUC of iDAV2 was not significantly different compared to iDAV1 (P = 0.174) but significantly different compared to GG (P &amp;lt; 0.05). For the &amp;gt; 42 years age group (n = 660) AUCs were 0.685 for iDAV1, 0.698 for iDAV2, and 0.682 for GS and were not significantly different among groups. The AUCs of iDAV1, iDAV2, and GG in all ages were 0.736, 0.720, and 0.702, respectively. iDAV2 were significantly higher than iDAV1 and GG (p &amp;lt; 0.05). Limitations, reasons for caution This study was based on minimal stimulation and natural cycle IVF treatment, and a freeze-all strategy whereby all transferred blastocysts had previously been vitrified. Therefore, we had only a few cycles with elective blastocyst transfer. In addition, this study was retrospective in nature. Wider implications of the findings For all age groups, iDAV2 had a higher AUC than iDAV1, although a significant difference was only observed for the young age group. This result suggests that the increased dataset used for the development of iDAV2 improved the performance of pregnancy prediction for SVBT in the deep-learning model. Trial registration number not applicable

P-126 The KAT-Score is a useful indicator for predicting ongoing pregnancy in mosaic risk assessment in PGT-A: a prospective study with single vitrified-warmed blastocyst transfer

Abstract Study question Does the mosaic risk score assessed by the KAT-Score correlate with clinical pregnancy and ongoing pregnancy? Summary answer A lower mosaic risk score assessed by the KAT-Score correlated with a higher ongoing pregnancy rate, but not with the clinical pregnancy rate. What is known already As the result of preimplantation genetic testing for aneuploidy (PGT-A), the result of analysis for mosaicism is obtained in addition to those for euploidy and aneuploidy. Viotti, et al. retrospectively analyzed 1000 mosaic embryo transfers, and showed that the rates of pregnancy and live birth differentiated stepwise depend on the type and level of mosaicism. Although it is possible to determine to the priority of embryo transfer according to the type of mosaicism, no prospective studies have been reported in which embryo transfer was performed using this method of selection. Study design, size, duration This is a prospective study conducted in a single IVF center between January 2020 and August 2022. A total of 104 single vitrified-warmed blastocyst transfer cycles were analyzed. The scoring of PGT-A embryos was assessed using the knowledge-based aneuploidy theoretical score (KAT-Score: Varinos Inc., Japan) in the range of 0 to 10. This study was approved by the Ethics Committee of the Institutional Review Board (IRB) of Kinutani Women’s Clinic, Hiroshima, Japan. Participants/materials, setting, methods The results of 104 vitrified-warmed single blastocyst transfers were classified into pregnancy (54 cycles) and non-pregnancy (50 cycles) groups. They were also classified into ongoing pregnancy (47 cycles) and non-ongoing pregnancy (57 cycles) groups. The correlations between KAT-Score and clinical pregnancy/ongoing pregnancy rates, were analyzed using the Wilcoxon signed-rank test and logistic regression analysis. Main results and the role of chance The KAT-Scores for 104 blastocysts ranged from 0 to 9. The distribution of scores is (KAT-Score 0: n = 43; 1-2: n = 21; 3-4: n = 4; 4-5: n = 16; 5-6: n = 7; 6-7: n = 5; 7-8: n = 6; 9: n = 2). First, mean values were compared between two different groups by use of the Wilcoxon signed-rank test. No significant difference in KAT-Score was observed between the pregnancy group and the non-pregnancy group (1.81 ± 2.42 vs. 2.78 ± 2.87; N.S.). On the other hand, the KAT-Score in the ongoing pregnancy group, was significantly lower than that in the non-ongoing pregnancy group (1.34 ± 1.98 vs. 3.04 ± 2.94; P &amp;lt; 0.01). Second, binary logistic regression analysis was used to calculate the area under the curve (AUC) as a predictive measure of clinical pregnancy or ongoing pregnancy. The KAT-Score assessment of PGT-A embryos was a predictive indicator of ongoing pregnancy (AUC = 0.67: P &amp;lt; 0.01), but not of clinical pregnancy (AUC = 0.59: N.S.). Multivariate logistic regression analysis, which included maternal age and morphological grade as confounding factors, showed that lower KAT-Scores correlated significantly with higher ongoing pregnancy rates (adjusted odds ratio: 0.77, 95% CI: 0.64−0.93, P &amp;lt; 0.01). In addition, the ongoing pregnancy rate from embryo transfer with euploid or mosaic embryos was not affected by maternal age or morphological grade. Limitations, reasons for caution The main limitation of this study is small sample size. Further research is required to gain a more complete understanding of whether the KAT-Score is associated with pregnancy and ongoing pregnancy. Wider implications of the findings This study suggests that the KAT-Score may be used as one of the indicators to predict ongoing pregnancy regardless of maternal age and morphological grade. The scoring of 104 embryo transfers by KAT-Score provides statistically valid evidence for ranking mosaic embryos in the infertility clinic. Trial registration number not applicable

P-192 Blastocyst collapse during embryonic development is a marker of low pregnancy potential, independent of other blastocyst evaluation criteria

Abstract Study question Is evaluation of blastocyst collapse during embryonic development an independent marker for ongoing pregnancy in single frozen-thawed blastocyst transfer cycles? Summary answer Collapse of blastocyst more than 20.4% of the area may be a marker of low ongoing pregnancy potential, independent of other evaluation criteria. What is known already Time-lapse monitoring revealed that a section of the extended trophectoderm (TE) is ruptured during development. This TE rupture causes an efflux of blastocoel fluid and a reduction in embryonic volume. This phenomenon is described as collapse. Several studies have reported that the collapse results in a low clinical and ongoing pregnancy potential for the blastocyst. However, the collapsed blastocysts were associated with poor morphological quality. Previous studies have not evaluated whether collapse is an independent predictor of pregnancy based on other blastocyst evaluation criteria. Therefore, it is necessary to determine whether blastocyst collapse is an independent predictor of ongoing pregnancy. Study design, size, duration This retrospective, single-center study was conducted at the TAKAHASHI WOMEN'S CLINIC from January, 2018 to December, 2020. All blastocysts were derived from the ICSI cycles. Time-lapse monitoring using Embryoscope + (Vitrolife) was used to observe the presence and degree of collapse. The degree of collapse was calculated from the embryonic volume at the maximum expansion and the lowest volume after collapse. We analyzed the relationship between 904 cycles of single vitrified-warmed blastocyst transfer and ongoing pregnancy. Participants/materials, setting, methods The ongoing pregnancy rates of collapsed and non collapsed blastocysts were compared using chi-squared test. The cut-off value of the degree of collapse for ongoing pregnancy was calculated using receiver operating characteristic (ROC) curve analysis. The effect of collapse above the cut-off value on ongoing pregnancy was examined using multivariate logistic regression analysis, including confounding factors (patient age, body mass index, inner cell mass (ICM) grade, TE grade, day of blastocyst formation, and expansion stage). Main results and the role of chance During the study period, 329 of the 904 transferred blastocysts exhibited collapse during time-lapse monitoring, and the degree of collapse ranged from 2.10% to 75.90%, with a median of 30.70%. In total, 575 transferred blastocysts were determined to be non collapsed. The mean patient age ( ± standard division) was 36.89 ± 4.77 years in the collapsed blastocyst group and 36.52 ± 4.42 years in the non collapsed blastocyst group (p = 0.151). The proportion of blastocysts with poor morphological grade (&amp;lt;BB ) was higher in the collapsed blastocysts group than in the non collapsed blastocysts group (32.5% vs. 17.91%, p &amp;lt; 0.0001). The ongoing pregnancy rate was significantly lower in the collapsed blastocysts group than in the non collapsed blastocysts group (45.4% vs. 34.0%, p = 0.0009). ROC curve analysis showed that the cut-off value for the degree of collapse for low pregnancy potential was 20.4%. Multivariate logistic analysis with confounding factors revealed that blastocyst collapse above the cut-off value (≥20.4%) had an effect on ongoing pregnancy (adjusted odds ratio: 0.53, 95% confidence interval: 0.34–0.82, p = 0.005) independent of ICM and TE grades, day of blastocyst formation, and expansion stage. Limitations, reasons for caution This retrospective study was conducted at a single fertility center. In addition, the analyzed blastocysts were derived only from the ICSI cycles. Therefore, it is necessary to analyze the effects of collapse in blastocysts derived from C-IVF cycles. Wider implications of the findings Our results demonstrate that ≥20.4% collapse may be an additional marker to consider when selecting blastocysts for transfer. If the blastocysts are of the same grade, it is better to select non collapsed embryos. Trial registration number not affect

Prolong cryopreservation duration negatively affects pregnancy outcomes of vitrified-warmed blastocyst transfers using an open-device system: A retrospective cohort study

ObjectiveTo investigate the impact of cryopreservation (CP) duration on pregnancy outcomes of vitrified-warmed blastocysts transfers using an open-device liquid-nitrogen (LN2) system. MethodsThis retrospective cohort study was conducted on 6327 first vitrified-warmed single blastocyst transfer cycles with autologous oocytes from January 2015 to December 2020. The CP duration was initially divided into six groups: Group I: 0–3 months (n = 4309); Group II: 4–6 months (n = 1061); Group III: 7–12 months (n = 304); Group IV: 13–24 months (n = 113); Group V: 25–72 months (n = 466); Group VI: 73–120 months (n = 74). Multivariate logistic regression was performed to evaluate the independent effect of CP duration on pregnancy outcomes. To further examine the time limit of vitrification, propensity score matching (PSM) was applied to compare pregnancy outcome of patients with storage duration of 25–120 months to those of 0–24 months. After that, pregnancy outcomes were compared among the subgroups of Group I’: 0–24 months, Group II’: 25–48 months, Group III’: 49–72 months, Group IV’: 73–120 months. Stratification analysis based on embryo quality was also performed. Primary outcomes were clinical pregnancy rate and live birth rate. Secondary outcomes were implantation, biochemical pregnancy rate, ongoing pregnancy rate and early miscarriage rate. ResultsLogistic regression demonstrated that the odds of pregnancy outcomes were similar across Group I to IV. However, the implantation rate, chances of biochemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth significantly decreased as the storage duration increased up to 25 months, while miscarriage rate did not significantly differ between groups. Subgroup analysis confirmed a dramatical decrease of clinical pregnancy and live birth rate when cryopreserved for more than 24 months. After that, the slope was relatively steady between 25 and 72 months, then steeply decreased again as CP reached 73–120 months. In addition, there was a more remarkable decline of pregnancy outcomes in the average quality embryo transfers than in the high quality embryo transfers as cryopreservation storage increased. ConclusionProlonged cryopreservation of vitrified blastocysts in an open-device LN2 system up to 24 months might negatively affect pregnancy outcomes. This negative impact progresses as storage duration increases, especially when exceeds 72 months. Average quality embryo appears to be less sustainable with long-term cryo-storage.

Clinical Usability of Embryo Development Using a Combined Qualitative and Quantitative Approach in a Single Vitrified-Warmed Blastocyst Transfer: Assessment of Pre-Vitrified Blastocyst Diameter and Post-Warmed Blastocyst Re-Expansion Speed

Improving the safety and efficacy of assisted reproductive technology programs has been a continuous challenge. Traditionally, morphological grading has been used for embryo selection. However, only a few studies have assessed the morphokinetic variables and morphological dynamics of blastocysts. In the present study, we aimed to perform a quantitative analysis of blastocyst diameter and re-expansion speed. This in-depth morphokinetic evaluation can correlate with currently observed pregnancy outcomes. In total, 658 single vitrified-warmed blastocyst transfer cycles were performed between October 2017 and December 2021, which were divided into four groups according to the pre-vitrified blastocyst diameter. After warming, the groups were subdivided according to the blastocyst re-expansion speed. These quantitative measurements were performed using a time-lapse system. Both diameter and speed are essential in determining the blastocyst quality, while age, day of freezing, and blastocyst quality are crucial from a clinical perspective. The application of both quantitative (diameter and speed) and qualitative (blastocyst quality scores) parameters can help evaluate the clinical usability of blastocysts. This method can prove useful for embryologists in counseling their patients and determining pregnancy patient-oriented strategies.

Morphometric assessment of blastocysts: relationship with the ongoing pregnancy rate

To explore a morphometric grading system for blastocysts that is associated with ongoing pregnancy. Cross-sectional study. None. All consecutive vitrified blastocysts at our center from July 2018 to November 2021 that were transferred in single blastocyst transfer cycles until January2022. None. The ongoing pregnancy rate after a single vitrified-warmed blastocyst transfer. Interobserver agreement on morphometric values among embryologists. Three morphometric variables (blastocyst diameter, area of inner cell mass [ICM], and the estimated trophectoderm cell count) were used to evaluate the expansion, ICM, and trophectoderm morphology. During the study period, 585 blastocysts were involved in this study. Of the 3 morphometric variables, ICM area (per 500 μm2, adjusted odds ratio, 1.19; 95% confidence interval, 1.09-1.30) and estimated trophectoderm cell count (per 10 cells, adjusted odds ratio, 1.25; 95% confidence interval, 1.12-1.39) were significantly associated with the ongoing pregnancy rate after adjustment for confounding factors. The ongoing pregnancy rate was 2.0% (1/49) with an ICM area of <2,500 μm2 and the estimated trophectoderm cell count <70. The ongoing pregnancy rate reached 47.8% (22/46) when the ICM area and the estimated trophectoderm cell count were >3,500 μm2 and >110, respectively. Interobserver agreement on the blastocyst diameter, ICM area, and the estimated trophectoderm cell count was excellent-to-good among 5 embryologists (intraclass correlation coefficients: 0.99, 0.87, and 0.91, respectively). Morphometric values of ICM and trophectoderm are promising predictors of pregnancy success. The high reproducibility suggests that the morphometric variables will contribute to identifying blastocysts with the highest developmental potential as well as those that will not result in a successful pregnancy.

Pregnancy outcome and follow-up of offspring of donor oocytes recipient from PCOS patients

BackgroundThe use of donated oocytes (DO) for in vitro fertilization(IVF) treatment in patients with infertility is generally recognized, and females with polycystic ovarian syndrome (PCOS) can participate in oocyte donation programs as donor patients. However, the pregnancy outcomes and offspring follow-up in patients with PCOS as the recipients are unclear. This study was to compare the pregnancy outcomes and follow-up of offspring in PCOS and non-PCOS receptor.MethodsThis was a retrospective cohort study of 62 patients undergoing the oocyte reception program were separated into 2 groups: Group I, PCOS oocyte recipients (n = 30); Group II, non-PCOS recipients (n = 32). Medical records were reviewed, and rates of fertilization, cleavage, high-quality embryos and blastocysts were compared between PCOS and non-PCOS groups. Rates of implantation, pregnancy, ectopic pregnancy, early abortion, multiple pregnancies, and offspring outcomes were calculated using the first single vitrified-warmed blastocyst transfer (SVBT) analysis between the groups.ResultsThe average recipient age and body mass index (BMI) of PCOS and non-PCOS patients was (36.3 ± 2.6 vs. 36.2 ± 2.8, and 23.4 ± 3.9 vs. 23.7 ± 4.0), respectively (P > 0.05). The fertilization, cleavage, high-quality embryos and blastocyst rates were not significantly different between the PCOS and non-PCOS groups. Rates of implantation, pregnancy, ectopic pregnancy, early abortion, and multiple pregnancies were not significantly different in SVBT between the PCOS and non-PCOS groups. The incidence of complications, such as pre-eclampsia or gestational diabetes, between PCOS and non-PCOS groups was similar (11.8% vs.11.1%, 5.9% vs.5.5%; P > 0.05). Preterm births were also similar (11.8% vs.16.7%, P > 0.05). Donor oocytes are more likely to be delivered via cesarean Sect. (80.0% vs. 86.7%: P > 0.05). The mean gestational age, birth weight, and height were comparable between the 2 groups during full-term delivery.ConclusionThere was no difference in the pregnancy outcomes and follow-up of the offspring between the PCOS and non-PCOS groups.

Endometrial preparation and maternal and obstetrical outcomes after frozen blastocyst transfer

Two types of endometrial preparation protocols are used for frozen embryo transfers in current practice: hormone replacement and the natural cycle. Endometrial preparation in the natural cycle reportedly increases the chances of live birth and decreases early pregnancy loss compared with that in the hormone replacement cycle. However, the influence of endometrial preparation on maternal and neonatal health remains unclear. This study aimed to investigate whether the differences between hormone replacement cycle and natural cycle influence perinatal outcomes and risk of congenital anomalies in frozen-thawed blastocyst transfer fetuses or births. Perinatal outcomes and congenital abnormalities were compared between the natural and hormone replacement cycles. According to the timing of ovulation, frozen-thawed blastocyst transfers in the natural cycle were classified into 2 patterns: on day 4.5 (ovulation 4.5) or day 5 (ovulation 5.0) after ovulation. When the serum luteinizing hormone level was not increased on the day of the trigger, a single vitrified-warmed blastocyst transfer was performed on day 7 after the trigger (ovulation 5.0). When the luteinizing hormone level was slightly increased on the day of trigger, single vitrified-warmed blastocyst transfer was performed on day 6 after the trigger (ovulation 5.0). In total, 67,018 cycles (ovulation 4.5, 29,705 cycles; ovulation 5.0, 31,995 cycles; hormone replacement, 5318 cycles) of frozen-thawed blastocyst transfer between January 2008 and December 2017 at Kato Ladies Clinic were retrospectively analyzed. During the study period, embryo cryopreservation was performed using a vitrification method in all cycles. Hormone replacement cycles were associated with a higher occurrence of hypertensive disorders of pregnancy (adjusted odds ratio, 2.16; 95% confidence interval, 1.66-2.81) and placenta accreta (adjusted odds ratio, 4.14; 95% confidence interval, 1.64-10.44) compared with the natural cycle. The risks of cesarean delivery (adjusted odds ratio, 1.93; 95% confidence interval, 1.78-2.18), preterm birth (adjusted odds ratio, 1.55; 95% confidence interval, 1.25-1.93), and low birthweight (adjusted odds ratio, 1.42; 95% confidence interval, 1.18-1.73) were also higher for hormone replacement cycles. No significant difference in the risk of congenital anomalies was observed between the 2 cycles. The risk of hypertensive disorders of pregnancy, placenta accreta, cesarean delivery, preterm delivery, and low birthweight was higher in hormone replacement cycles than in natural cycles, whereas the risk of congenital anomalies was similar between both cycles. Further follow-up is needed to investigate these risks and to explore alternative endometrial preparation methods.

Correlation between an annotation-free embryo scoring system based on deep learning and live birth/neonatal outcomes after single vitrified-warmed blastocyst transfer: a single-centre, large-cohort retrospective study

ProposeDoes an annotation-free embryo scoring system based on deep learning and time-lapse sequence images correlate with live birth (LB) and neonatal outcomes?MethodsPatients who underwent SVBT cycles (3010 cycles, mean age: 39.3 ± 4.0). Scores were calculated using the iDAScore software module in the Vitrolife Technology Hub (Vitrolife, Gothenburg, Sweden). The correlation between iDAScore, LB rates, and total miscarriage (TM), including 1st- and 2nd-trimester miscarriage, was analysed using a trend test and multivariable logistic regression analysis. Furthermore, the correlation between the iDAScore and neonatal outcomes was analysed.ResultsLB rates decreased as iDAScore decreased (P < 0.05), and a similar inverse trend was observed for the TM rates. Additionally, multivariate logistic regression analysis showed that iDAScore significantly correlated with increased LB (adjusted odds ratio: 1.811, 95% CI: 1.666–1.976, P < 0.05) and decreased TM (adjusted odds ratio: 0.799, 95% CI: 0.706–0.905, P < 0.05). There was no significant correlation between iDAScore and neonatal outcomes, including congenital malformations, sex, gestational age, and birth weight. Multivariate logistic regression analysis, which included maternal and paternal age, maternal body mass index, parity, smoking, and presence or absence of caesarean section as confounding factors, revealed no significant difference in any neonatal characteristics.ConclusionAutomatic embryo scoring using iDAScore correlates with decreased miscarriage and increased LB and has no correlation with neonatal outcomes.

P-754 Perinatal outcomes and congenital anomalies after clomiphene citrate based minimal ovarian stimulation in vitro fertilisation stratified by embryo transfer method: a 10-year cohort study

Abstract Study question Is the embryo transfer method associated with perinatal outcomes and congenital anomalies after minimal ovarian stimulation in vitro fertilisation (IVF) with clomiphene citrate (CC)? Summary answer Single vitrified-warmed blastocyst transfers in natural cycles had a lower incidence of pregnancy complications compared to single fresh cleaved embryo transfers after CC-based ovarian stimulation. What is known already Pregnancies resulting from IVF are associated with a higher risk of adverse perinatal outcomes compared to spontaneous conception; therefore, the next focus in reproductive medicine is to assess whether the increased risks are attributable to the IVF. Perinatal outcomes and congenital anomalies should be considered in addition to pregnancy outcomes in selecting the embryo transfer method. However, studies describing the influence of transfer methods on perinatal and maternal outcomes are limited. Study design, size, duration This study retrospectively analysed a single centre 10-year cohort. A total of 82,491 clinical records of women who underwent oocyte retrieval during a CC-based minimal stimulation cycle followed by single fresh cleaved embryo transfer (SFCT), single vitrified-warmed cleaved embryo transfer (SVCT), or single vitrified-warmed blastocyst transfer (SVBT) at the Kato Ladies Clinic between January 2008 and December 2017 were retrospectively analysed. Participants/materials, setting, methods The oocyte retrievals were performed in CC-based minimal ovarian stimulation. The embryos were transferred 2–3 days after retrieval, or vitrified at the cleavage or blastocyst stages. The vitrified embryos were warmed and transferred within the natural cycles. Perinatal outcomes and congenital anomalies were stratified by the transfer method. Multivariate logistic regression analysis was performed to evaluate the effect of transfer methods on pregnancy complications and congenital anomalies. Main results and the role of chance The perinatal outcomes and congenital anomalies in 19,069 singleton pregnancies were analysed. Multivariate logistic regression analysis revealed that the incidence of hypertensive disorders of pregnancy was significantly lower in the SVBT group compared with the SFCT group (adjusted odds ratio [AOR], 0.628; P &amp;lt; 0.0001). The incidence of low-lying placenta (AOR 0.359 P = 0.0483; AOR 0.452 P &amp;lt; 0.0001, respectively) and placenta previa (AOR 0.300 P = 0.0021; AOR 0.542 P &amp;lt; 0.0001, respectively) were lower in the SVCT and SVBT groups than in the SFCT group. The rate of preterm delivery was lower in SVBT compared with SFCT (AOR 0.732 P &amp;lt; 0.0001). The rate of low birth weight was significantly lower after SVCT and SVBT, compared with the SFCT group (AOR 0.751; P = 0.0261: AOR, 0.560; P &amp;lt; 0.0001: respectively). A lower incidence of small for gestational age (AOR 0.720 P = 0.0436; AOR 0.494 P &amp;lt; 0.0001, respectively) and higher incidence of large for gestational age (AOR 1.287 P = 0.0332; AOR 1.706 P &amp;lt; 0.0001, respectively) were observed in the SVCT and SVBT groups compared to the SFCT group. The incidence of each congenital anomaly was similar among the groups. Limitations, reasons for caution The data was collected through self-reported parental questionnaires on neonatal outcomes and congenital malformations. Furthermore, this study was retrospective in nature; further studies are necessary to ascertain the generalisability of these findings to other clinics with different protocols and/or patient demographics. Wider implications of the findings This study demonstrated reassuring outcomes for SVBT, in terms of a lower incidence of pregnancy complications compared with SFCT. Our findings provide valuable knowledge to improve perinatal outcomes in CC-based stimulation and to inform couples of the possible benefits and harms of each type of embryo transfer method. Trial registration number not applicable