Evaluating the heterogeneous effect of extended culture to blastocyst transfer on the implantation outcome via causal inference in fresh ICSI cycles
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In IVF treatments, extended culture to single blastocyst transfer is the recommended protocol over cleavage-stage transfer. However, evidence-based criteria for assessing the heterogeneous implications on implantation outcomes are lacking. The purpose of this work is to estimate the causal effect of blastocyst transfer on implantation outcome.Keywords:
Blastocyst Transfer
Abstract Background High-quality single blastocyst transfer (SBT) is increasingly recommended to patients because of its acceptable pregnancy outcomes and significantly reduced multiple pregnancy rate compared to double blastocyst transfer (DBT). However, there is no consensus on whether this transfer strategy is also suitable for poor-quality blastocysts. Moreover, the effect of the development speed of poor-quality blastocysts on pregnancy outcomes has been controversial. Therefore, this study aimed to explore the effects of blastocyst development speed and morphology on pregnancy and neonatal outcomes during the frozen embryo transfer (FET) cycle of poor-quality blastocysts and to ultimately provide references for clinical transfer strategies. Methods A total of 2,038 FET cycles of poor-quality blastocysts from patients 40 years old or less were included from January 2014 to December 2019 and divided based on the blastocyst development speed and number of embryos transferred: the D5-SBT ( n = 476), D5-DBT ( n = 365), D6-SBT ( n = 730), and D6-DBT ( n = 467) groups. The SBT group was further divided based on embryo morphology: D5-AC/BC ( n = 407), D5-CA/CB ( n = 69), D6-AC/BC ( n = 580), and D6-CA /CB ( n = 150). Results When blastocysts reach the same development speed, the live birth and multiple pregnancy rates of DBT were significantly higher than those of SBT. Moreover, there was no statistical difference in the rates of early miscarriage and live birth between the AC/BC and CA/CB groups. When patients in the SBT group were stratified by blastocyst development speed, the rates of clinical pregnancy (42.44 % vs. 20.82 %) and live birth (32.35 % vs. 14.25 %) of D5-SBT group were significantly higher than those of D6-SBT group. Furthermore, for blastocysts in the same morphology group (AC/BC or CA/CA group), the rates of clinical pregnancy and live birth in the D5 group were also significantly higher than those of D6 group. Conclusions For poor-quality D5 blastocysts, SBT can be recommended to patients because of acceptable pregnancy outcomes and significantly reduced multiple pregnancy rate compared with DBT. For poor-quality D6, the DBT strategy is recommended to patients to improve pregnancy outcomes. When blastocysts reach the same development speed, the transfer strategy of selecting blastocyst with inner cell mass “C” or blastocyst with trophectoderm “C” does not affect the pregnancy and neonatal outcomes.
Blastocyst Transfer
Live birth
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This preliminary study reports the results obtained from a patient group in which blastocyst culture and transfer were performed, and discusses the advantages and disadvantages of introducing blastocyst transfer in a clinic. Twenty-six patients who had failed to achieve a pregnancy in previous in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) treatments were offered the choice of a fresh cycle with culture to the blastocyst stage. Of the 26 patients who elected to attempt blastocyst culture, 11 opted to have transfer on day 2 or day 3 due to low numbers of embryos. Of the 15 patients who proceeded to blastocyst culture, 46.2% of the embryos cultured reached the blastocyst stage or later and eight of the patients achieved a clinical pregnancy. More oocytes were collected in this patient group, hence the chances of obtaining blastocysts were higher. Offering blastocyst culture to patients with a reasonable chance of success who have had previous multiple assisted reproduction failures is an acceptable way of introducing blastocyst culture into practice.
Blastocyst Transfer
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Abstract Background Day 5 (D5) blastocyst is generally given priority to transfer than Day 6 (D6) blastocyst, however, which one should be prioritized to transfer when only low-grade D5 and high-grade D6 blastocysts are available? Methods A large retrospective cohort study was carried out to evaluate the live birth rate (LBR) following D5 blastocyst and excellent D6 blastocyst in single frozen-thawed blastocyst transfer (FBT) during Jan 2014 and Dec 2018. The biopsied blastocysts form consecutive PGT-A case series during Feb 2013 to Dec 2021 were performed as a supplementary analysis. Results The LBR was highest in high-grade D5 blastocyst (57.60%) and lowest in low-grade D6 blastocyst (29.72%, vs high-grade D5, aOR 0.38, 95%CI 0.30–0.48, p < 0.001). The LBR achieved in high-grade D6 blastocyst transfer was significantly higher than low-grade D5 blastocyst (50.43% vs 40.70%, aOR 1.54, 95%CI 1.05–2.26, p = 0.027), and is comparable with that in high-grade D5 blastocyst (50.43% vs 57.60%, aOR 0.89, 95%CI 0.61–1.32, p = 0.568). There were no significant differences in preterm birth rate, very preterm birth rate, mean live birth weight, birth weight < 1500g and > 4000g between four cohorts. As for aneuploidy analysis in PGT, there were 54.55% of euploid blastocysts (30/55) among high-grade D6 blastocysts, significantly higher than 41.39% of euploid blastocysts (565/1365) among low-grade D5 blastocyst (p < 0.001). Conclusions Our data suggested Day 6 blastocyst with high morphology grading should be preferred than Day 5 blastocyst with low morphology grading when selecting blastocyst transfer to short the time of conceiving. Trial registration: This study was approved by the hospital institutional ethics committee (No. 2021002).
Blastocyst Transfer
Live birth
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Blastocyst Transfer
Live birth
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Abstract Study question What is the clinical outcome of transferring a mosaic blastocyst versus a euploid blastocyst in single frozen blastocyst transfer (sFBT) cycles? Summary answer Single mosaic blastocyst transfer has similar clinical outcome to single euploid blastocyst transfer. What is known already Embryonic mosaicism occurs when there are two or more distinct cell lines found in preimplantation embryos derived from IVF. Data from recent studies show that mosaic blastocysts have the potential to implant and can result in healthy live births. As a result, patients now have the option of transferring mosaic blastocyst when they do not have any euploid blastocyst available for transfer. However, the clinical outcome of transferring mosaic blastocyst has not been definitively reported. Thus, a retrospective study was conducted to compare the clinical outcome of mosaic sFBT and euploid sFBT. Study design, size, duration A total of 602 patients underwent frozen blastocyst transfer in Alpha IVF from January to October 2019 and had their blastocysts screened for aneuploidy. These patients were divided into 2 groups: 26 patients with mosaic blastocysts transferred (Group A, age ranged 19–44), and 576 patients with euploid blastocysts transferred (Group B, age ranged 21–44). The mean age of patients from Group A and B were 34.0 and 32.8 respectively (p > 0.05). Participants/materials, setting, methods All samples had their DNA libraries constructed for sequencing using Next Generation Sequencing according to manufacturer’s specification (IonTorrent, USA). All blastocysts were frozen for subsequent sFBT cycle (Cryotech, Japan). All thawed blastocysts for sFBT survived with morphologically intact inner cell mass and trophectoderm cells. The importance of antenatal confirmation of the fetal chromosome status was emphasized in patients from Group A. The clinical outcomes of both groups were analysed and compared. Main results and the role of chance No significant differences were seen in the clinical pregnancy and implantation rate of Group A and B (65.4% vs 63.0%; p > 0.05). The miscarriage rate of Group A and B were 23.5% and 14.0% respectively. Albeit the higher miscarriage rate in Group A, there was no statistical significance between these two groups (p > 0.05). Group A was further divided into two subgroups, Subgroup A1: low risk mosaic blastocyst transfer; Subgroup A2: high risk mosaic blastocyst transfer. In the comparison of Group A subgroups, the clinical pregnancy and implantation of Group A1 is higher than Group A2 (76.9% vs 44.4%). In addition, the miscarriage rate of Group A1 and A2 were 23.1% and 0.0% respectively. Interestingly, there was no statistical significance in clinical pregnancy rate, implantation rate and miscarriage rate between these two subgroups. Limitations, reasons for caution This is a retrospective study and the sample size was comparatively smaller in the mosaic blastocyst transfer group than the euploid blastocyst transfer group. Further studies with a larger sample size should be carried out to ascertain the clinical outcome. Wider implications of the findings: Single mosaic blastocyst transfer has similar clinical outcome to single euploid blastocyst transfer. Thus, mosaic blastocyst can be considered for transfer when no euploid blastocyst are available. Nevertheless, stringent antenatal surveillance for chromosomal abnormalities to confirm the chromosomal status of the fetus must be followed. Trial registration number Not applicable
Blastocyst Transfer
Live birth
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Objective To evaluate the effectiveness of the blastocyst culture and transfer compared with the cleavage stage transfer.Methods Patients were recruited into this study from those embarking on IVF treatment for the reasons of fallopian tube and male infertility.The cleavage stage transfers were performed on 110 cases and the blastocyst cultures and transfers on 57 cases.The numbers of obtaining and fertilized ovum,embryonic implantation and clinical pregnant rates as well as the blastocyst formation rate、 the relationship between the embryo numbers of each transfer and the multiplets and clinical pregnant rates were evaluated.Results The numbers of obtaining and fertilized ovum rates in the blastocyst group was higher than that in the blastocyst group(4.98 and 3.98,respectively).The blastocyst formation rate was 32.9% using G1/G2 sequential culture media.The embryonic implantation rate and clinical pregnant rates were significantly higher in the blastocyst group than that in the cleavage stage group(31.2%,42.1% and 11.5%,25.5%,respectively).There was no significantly difference between transfer 2 or 3 blastocystes.It appears that the numbers of twins was reduced in transfer 2 blastocystes.Conclusion The results of our study confirmed that the blastocyst transfer has more advantages than the cleavage stage transfer in rising the embryonic implantation rate and clinical pregnant rate.Transfer 2 blastocyst is best choice for IVF-ET.
Blastocyst Transfer
Cleavage (geology)
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Abstract Background: High-quality single blastocyst transfer (SBT) is increasingly recommended to patients because of its acceptable pregnancy outcomes and significantly reduced multiple pregnancy rate compared to double blastocyst transfer (DBT). However, there is no consensus on whether this transfer strategy is also suitable for poor-quality blastocysts. Moreover, the effect of the development speed of poor-quality blastocysts on pregnancy outcomes has been controversial. Therefore, this study aimed to explore the effects of blastocyst development speed and morphology on pregnancy and neonatal outcomes during the frozen embryo transfer (FET) cycle of poor-quality blastocysts and to ultimately provide references for clinical transfer strategies. Methods: A total of 2,038 FET cycles of poor-quality blastocysts were analyzed from January 2014 to December 2019 and divided based on the blastocyst development speed and number of embryos transferred: the D5-SBT (n=476), D5-DBT (n=365), D6-SBT (n=730), and D6-DBT (n=467) groups. The SBT group was further divided based on embryo morphology: D5-AC/BC (n=407), D5-CA/CB (n=69), D6-AC/BC (n=580), and D6-CA /CB (n=150). Results: When blastocysts reach the same development speed, the live birth and multiple pregnancy rates of DBT were significantly higher than those of SBT. Moreover, there was no statistical difference in the rates of early miscarriage and live birth between the AC/BC and CA/CB groups. When patients in the SBT group were stratified by blastocyst development speed, the rates of clinical pregnancy (42.44% vs. 20.82%) and live birth (32.35% vs. 14.25%) of D5-SBT group were significantly higher than those of D6-SBT group. Furthermore, for blastocysts in the same morphology group (AC/BC or CA/CA group), the rates of clinical pregnancy and live birth in the D5 group were also significantly higher than those of D6 group. Conclusion: For poor-quality D5 blastocysts, SBT can be recommended to patients because of acceptable pregnancy outcomes and significantly reduced multiple pregnancy rate compared with DBT. For poor-quality D6, the DBT strategy is recommended to patients to improve pregnancy outcomes. When blastocysts reach the same development speed, the transfer strategy of selecting blastocyst with inner cell mass “C” or blastocyst with trophectoderm “C” does not affect the pregnancy and neonatal outcomes.
Blastocyst Transfer
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Blastocyst Transfer
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The advantages of blastocyst transfer in mid-good responders include a reduction in multiple pregnancies due to single good-quality blastocyst transfer and an elevation of implantation and ongoing pregnancy rates due to establishment of the vitrification method. However, evidence is lacking as to whether blastocyst culture is effective in poor responders. In fact, few centers have adopted blastocyst transfer for all patients. Blastocyst development rate is around 50-60%. Several kinds of commercial sequential media are currently available and almost all Assisted Reproductive Technology (ART) units use these for treatment of patients. However, the period in which these media can be used is limited to 26-70 days according to the instructions provided by manufacturers. The half-life of pyruvate and antibiotics is supposedly short, and vitamins and hormones are unstable. Ideally, centers would make and use their own media within 72 h. In the near future, optimal ovarian stimulation, culture conditions, embryo transfer and luteal support should enable the possibility of providing healthy pregnancy following single blastocyst transfer in almost all patients.
Blastocyst Transfer
Vitrification
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