Frozen-thawed Single Blastocyst Transfer Cycles Research Articles

Trophectoderm grade is associated with the risk of placenta previa in frozen-thawed single-blastocyst transfer cycles.

Do obstetric and perinatal complications vary according to different blastocyst developmental parameters after frozen-thawed single-blastocyst transfer (SBT) cycles? Pregnancies following the transfer of a blastocyst with a grade C trophectoderm (TE) were associated with an increased risk of placenta previa compared to those with a blastocyst of grade A TE. Existing studies investigating the effect of blastocyst morphology grades on birth outcomes have mostly focused on fetal growth and have produced conflicting results, while the risk of obstetric complications has rarely been reported. Additionally, growing evidence has suggested that the appearance of TE cells could serve as the most important parameter for predicting implantation and live birth. Given that the TE ultimately develops into the placenta, it is plausible that this independent predictor may also impact placentation. This retrospective cohort study at a tertiary-care academic medical center included 6018 singleton deliveries after frozen-thawed SBT cycles between January 2017 and December 2021. Singleton pregnancies were grouped into two groups according to blastocyst developmental stage (Days 5 and 6), four groups according to embryo expansion (Stages 3, 4, 5, and 6), three groups according to inner cell mass (ICM) quality (A, B, and C), and three groups according to TE quality (A, B, and C). The main outcomes included pregnancy-induced hypertension, preeclampsia, gestational diabetes mellitus, preterm premature rupture of membrane, placenta previa, placental abruption, placenta accreta, postpartum hemorrhage, preterm birth, low birth weight, small for gestational age, and birth defects. Multivariate logistic regressions were performed to evaluate the effect of blastocyst developmental stage, embryo expansion stage, ICM grade, and TE grade on measured outcomes adjusting for potential confounders. No association was found between blastocyst developmental stage and obstetric or perinatal outcomes both before and after adjusting for potential confounders, and similar results were found with regard to embryo expansion stage and ICM grade. Meanwhile, the incidence of placenta previa derived from a blastocyst with TE of grade C was higher compared with those derived from a blastocyst with TE of grade A (1.7%, 2.4%, and 4.0% for A, B, and C, respectively, P = 0.001 for all comparisons). After adjusting for potential covariates, TE grade C blastocysts had 2.81 times the likelihood of resulting in placenta previa compared to TE grade A blastocysts (adjusted odds ratio 2.81, 95% CI 1.11-7.09). No statistically significant differences were detected between any other measured outcomes and TE grades both before or after adjustment. The study is limited by its retrospective, single-center design. Additionally, although the sample size was relatively large for the study group, the sample size for certain subgroups was relatively small and lacked adequate power, particularly the ICM grade C group. Therefore, these results should be interpreted with caution. The study extends our knowledge of the potential downstream effect of TE grade on placental abnormalities. This study was supported by the National Key Research and Development Program of China (2023YFC2705500, 2023YFC2705501, 2023YFC2705505, 2019YFA0802604); National Natural Science Foundation of China (82130046, 82320108009, 82371660, 32300710); Shanghai leading talent program, Innovative research team of high-level local universities in Shanghai (SHSMU-ZLCX20210201, SHSMU-ZLCX20210200, SHSMU-ZLCX20180401), Shanghai Jiaotong University School of Medicine Affiliated Renji Hospital Clinical Research Innovation Cultivation Fund Program (RJPY-DZX-003), Science and Technology Commission of Shanghai Municipality (23Y11901400), Shanghai's Top Priority Research Center Construction Project (2023ZZ02002), and Three-Year Action Plan for Strengthening the Construction of the Public Health System in Shanghai (GWVI-11.1-36). The authors have no conflicts of interest to declare. N/A.

P-153 Optimizing clinical outcomes in single vitrified-thawed blastocyst transfer cycles: impact of blastocyst re-expansion status

Abstract Study question is the blastocyst re-expansion status according to the thawing-transfer time interval related to the clinical outcomes in a single frozen-thawed blastocyst transfer cycles? Summary answer The post-thawing blastocyst shrinkage is linked to lower clinical outcomes, and minimizing the time between thawing and transfer optimizes outcomes especially for shrunken blastocysts. What is known already • A reduced ART outcome was observed with the use of shrunken post-warming blastocysts (Ito et al., 2023) • The spontaneous blastocyst shrinkage observed during in vitro embryonic development is considered as a negative prognosis factor for implantation (Sciorio et al., 2020) • The blastocyst’s re-expansion level after thawing proves to be the best post-thaw parameter for the prediction of live birth (The Vienna consensus., 2017. Ahlstrom et al., 2013). • The fast blastocele re-expansion seems to have a predictive value for implantation in frozen-thawed blastocyst transfer cycle (Shu et al., 2009). Study design, size, duration This was a retrospective study of 577 single frozen-thawed blastocyst transfer cycles from January 2022 to April 2023. Participants/materials, setting, methods Only B4 and B5 blastocyst quality obtained in day-5 were included in this study. The morphological characteristics were evaluated: after thawing (T0) and at Transfer time (TR). Blastocysts with 50% reduction of blastocele were classified “Shrunken”, the rest are “re-expanded”. and categorized into Group-1: re-expanded at T0 (n = 173); Group-2: shrunken at T0 and re-expanded at TR (n = 135); Group-3: shrunken at T0 and TR (n = 199). Statistical tests: chi-square, T-test and Mann-Whitney. (Statistical significance p < 0.05*). Main results and the role of chance Clinical outcomes of re-expanded blastocysts comparing to shrunken blastocysts at TR were respectively 42.21% versus 32.71% for pregnancy rate (PR) (p < 0.007),39.61% versus 30.48% for implantation rate (IR) (p < 0.02) and 35.71% versus 22.30% for life birth rate (LBR) (p < 0.004), a significantly higher outcomes were observed for re-expanded blastocysts. The miscarriage rate decreased from 25.00% to 9.23% (p < 0.001). The transfer of shrunken blastocysts in an interval of time within 1 hour or less comparing to more than 1 hour between T0 and TR showed the following results: PR = 40.82% versus 28.07% (p < 0.032), IR = 39.81% to 25.10%, (p < 0.02) and LBR = 26.53% versus 19.88% (p < 0.2). a significantly higher clinical outcomes were observed for shrunken blastocysts transferred within 1 hour or less. Group analysis: the PR, IR and LBR significantly increased for Group-1 comparing to Group 2. For Group-3, shrunken blastocysts at TR had the lower outcomes. (respectively p = 0.003; 0.017; 0.0002) Limitations, reasons for caution It is an ongoing retrospective observational study. Blastocysts with a low quality (B3 or less) were excluded from this study how limit our ability to extend the findings to low morphology degrees not covered by this research. Wider implications of the findings The management of frozen blastocyst transfers in IVF laboratories have to take into consideration in addition to the classic morphological evaluation, the blastocoele re-expansion state and the time interval between thawing and transfer to optimize the transfer outcomes. Trial registration number not applicable

Effect of development speed and quality of blastocyst on singleton birthweight in single frozen-thawed blastocyst transfer cycles.

Assisted reproductive technology (ART) has revolutionized infertility treatment, leading to a surge in ART-conceived children. Despite its success, ART-born offspring face higher risks of preterm birth (PTB), low birth weight (LBW), and small for gestational age (SGA). The mechanisms behind these outcomes remain unclear, partly attributed to multiple embryo transfers. Recent advancements advocate single blastocyst transfers for improved outcomes. However, the influence of blastocyst quality and development speed on neonatal outcomes is underexplored. This study investigated whether blastocyst development speed and quality affect singleton birthweight when the blastocyst is selected for single frozen-thawed blastocyst transfer (FBT). Data from patients who performed an FBT cycle at our center from July 2011 to June 2021 were collected and analyzed. Based on the inclusion and exclusion criteria, 420 single FBT cycles were assessed. The women were divided into four groups, Group A (day 5, good-quality blastocysts), Group B (day 5, non-good-quality blastocysts), Group C (day 6, good-quality blastocysts), and Group D (day 6, non-good-quality blastocysts) according to the developmental speed and quality of the transferred blastocyst. The birthweight was relatively the highest in Group A, which developed rapidly and transferred good quality blastocysts. However, no significant difference existed among the groups (P>0.05). The prevalence of premature birth (PTB), low birth weight (LBW), very low birth weight (VLBW), or high birth weight (HBW) was similar among the four groups (P > 0.05). No correlation existed between birth weight and blastocyst development speed or quality after adjusting for possible confounders (P > 0.05 respectively). However, the difference in the proportion of males born among the four groups was significant, especially in Group D, which was significantly lower than that in Group A (adjusted odds ratio = 0.461, 95% confidence interval: 0.230-0.921, P< 0.05). This retrospective cohort study suggests that the combined effect of blastocyst development speed and quality on neonatal birthweight is insignificant. The transfer of slow-growing, non-good-quality blastocysts increases the chance of a female baby being born.

Adverse maternal and neonatal outcomes of preimplantation genetic testing with trophectoderm biopsy: a retrospective cohort study of 3373 intracytoplasmic sperm injection single frozen-thawed blastocyst transfer cycles.

To investigate whether trophectoderm biopsy increases the risk of adverse maternal and neonatal outcomes in intracytoplasmic sperm injection (ICSI) single frozen-thawed blastocyst transfer cycles. This respective cohort study enrolled 3373 ICSI single frozen-thawed blastocyst transfer cycles with and without trophectoderm biopsy. Statistical methods including univariate logistic regression analysis, multivariate logistic regression analysis, and stratified analyses were performed to explore the impact of trophectoderm biopsy on adverse maternal and neonatal outcomes. The rates of adverse maternal and neonatal outcomes were comparable between the two groups. Univariate analysis showed that the live birth rate (45.15% vs. 40.75%; P = 0.010) in the biopsied group was statistically higher than that in the unbiopsied group, and the rates of miscarriage (15.40% vs. 20.00%; P = 0.011) and birth defects (0.58% vs. 2.16%; P = 0.007) were statistically lower in the biopsied group. After adjusting for confounding factors, the rates of miscarriage (aOR = 0.74; 95% CI = 0.57-0.96; P = 0.022) and birth defects (aOR = 0.24, 95% CI = 0.08-0.70, P = 0.009) in the biopsied group were significantly lower than those in the unbiopsied group. Stratified analyses showed that the birth defects rate after biopsy was significantly reduced in the subgroups of age < 35years old, BMI ≥ 24kg/m2, artificial cycle with downregulation, poor-quality blastocysts, and Day 5 poor-quality blastocysts. Preimplantation genetic testing (PGT) with trophectoderm biopsy does not increase the risk of adverse maternal and neonatal outcomes in ICSI single frozen-thawed blastocyst transfer cycles, and PGT can effectively reduce the rates of miscarriage and birth defects.

P-269 trophectoderm grade is associated with the risk of placenta previa in frozen-thawed single blastocyst transfer cycles

Abstract Study question Dose obstetric and perinatal complications differ among different blastocyst developmental parameters after frozen-thawed single blastocyst transfer (SBT) cycles? Summary answer Blastocysts with grade C trophectoderm (TE) were associated with an increased risk of placenta previa compared to those with grade A TE. What is known already Existing studies investigating the effect of blastocyst morphology grades on birth outcomes have mostly focused on fetal growth and have produced conflicting results, while the risk of obstetric complications has rarely been reported. Additionally, growing evidence have suggested that the appearance of TE cells could serve as the most important parameter for predicting implantation and live birth. Given that the TE ultimately develops into the placenta, it is plausible that this independent predictor may also impact placentation. Study design, size, duration This was a retrospective cohort study conducted at a single tertiary-care academic reproductive center. A total of 6168 patients who underwent frozen-thawed SBT and resulted in singleton delivery beyond 20 weeks of gestation between January 2017 and December 2021 were analyzed. Participants/materials, setting, methods Main outcomes included placenta previa, placental abruption, placenta accreta, pregnancy-induced hypertension (PIH), preeclampsia, preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA). Multivariate logistic regressions were performed to evaluate the effect of blastocyst developmental stage (day 5 and 6), embryo expansion stage (stages 3, 4, 5 and 6), inner cell mass (ICM) grade (A, B and C), and TE grade (A, B and C) on measured outcomes adjusting for potential confounders. Main results and the role of chance The overall rates of placenta previa, placental abruption, placenta accreta, PIH, preeclampsia, PTB, LBW and SGA was 2.8% (n = 173), 0.4% (n = 26), 1.3% (n = 83), 5.3% (n = 328), 4.3% (n = 267), 6.8% (n = 417), 3.7% (n = 230), and 2.8% (n = 172), respectively. Specifically, the incidence of placenta previa derived from blastocyst with TE of grade C was higher compared with those derived from blastocyst with TE of grade A (1.8%, 2.5% and 3.9% for A, B and C, respectively, P = 0.003 for all comparisons). No such differences were observed for any other outcomes. After adjusting for potential covariates (maternal age, maternal BMI, maternal education, duration of infertility, gravidity, parity, previous caesarean section, infertility diagnosis, IVF or ICSI, previous embryo transfer, and type of endometrial preparation), TE grade C blastocyst had 2.58 times the likelihood of resulting in the risk of placenta previa compared to TE grade A blastocysts (adjusted odds ratio [AOR] 2.58, 95% confidence interval [CI] 1.05-6.31). No statistically significant associations were detected between any other measured outcomes and blastocyst developmental parameters. Furthermore, when restricted to pregnancies above 28 gestational weeks, the risk of placenta previa remained significantly higher with TE of grade C (AOR 2.56, 95% CI 1.05-6.27) than with TE of grade A. Limitations, reasons for caution The retrospective design, lack of controlling for residual confounding factors, and inter-observer variability limited this study. Wider implications of the findings The study extends our knowledge of the potential downstream effect of TE grade on placental abnormalities. 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

Association between endometrial blood and clinical outcome in frozen single blastocyst transfer cycles.

Background: The success of embryo transfer cycle depends mainly on the quality of embryo and endometrial receptivity. Ultrasound examination is still the most widely used non-invasive evaluation method for its advantages of convenience, non-invasiveness and repeatability. Ultrasound-measured endometrial blood flow is one of the important evaluation indicators of morphology. Aims: To investigate the effect of the number of endometrial blood flow branches on pregnancy outcome of frozen-thawed embryo transfer cycles which have undergoing hormone replacement therapy (HRT-FET). Material and methods: A retrospective cohort study was performed looking at a total of 1390 HRT-FET cycles from our reproductive medicine center between January 2017 to December 2021, which transferred one blastocyst frozen on day 5 with good quality in morphology. Associations between endometrial blood flow branches and pregnancy outcomes were evaluated with multivariable linear regression analysis. Results: The number of endometrial blood flow branches was independently associated with clinical pregnancy (OR 1.10; 95% CI 1.02-1.20). After adjusting for potential confounders, the effect size (odds ratio) was 1.09 (95% CI 1.00-1.19), and the results showed that the clinical pregnancy rate and live birth rate of T2 and T3 groups were significantly higher than those in group T1 (p < 0.05). Subgroup analysis showed that a consistent association between the endometrial blood flow branches and clinical pregnancy in all subgroups. Conclusion: Our study provided evidence for the influence of endometrial blood flow on pregnancy outcomes. There may be an independent association between the number of endometrial blood flow branches and pregnancy outcomes in frozen-thawed single blastocyst transfer cycles.

Trophectoderm biopsy is associated with adverse obstetric outcomes rather than neonatal outcomes

BackgroundWith the wide application of preimplantation genetic testing (PGT) with trophectoderm (TE) biopsy, the safety of PGT has always been a concern. Since TE subsequently forms the placenta, it is speculated that the removal of these cells was associated with adverse obstetrical or neonatal outcomes after single frozen-thawed blastocyst transfer (FBT). Previous studies report contradictory findings with respect to TE biopsy and obstetric and neonatal outcomes.MethodsWe conducted a retrospective cohort study including 720 patients with singleton pregnancies from single FBT cycles who delivered at the same university-affiliated hospital between January 2019 and March 2022. The cohorts were divided into two groups: the PGT group (blastocysts with TE biopsy, n = 223) and the control group (blastocysts without biopsy, n = 497). The PGT group was matched with the control group by propensity score matching (PSM) analysis at a ratio of 1:2. The enrolled sample sizes in the two groups were 215 and 385, respectively.ResultsPatient demographic characteristics were comparable between the groups after PSM except for the proportion of recurrent pregnancy loss, which was significantly higher in the PGT cohort (31.2 vs. 4.2%, P < 0.001). Patients in the PGT group had significantly higher rates of gestational hypertension (6.0 vs. 2.6%, adjusted odds ratio (aOR) 2.91, 95% confidence interval (CI) 1.18–7.18, P = 0.020) and abnormal umbilical cord (13.0 vs. 7.8%, aOR 1.94, 95% CI 1.08–3.48, P = 0.026). However, the occurrence of premature rupture of membranes (PROM) (12.1 vs. 19.7%, aOR 0.59, 95% CI 0.35–0.99, P = 0.047) was significantly lower in biopsied blastocysts than in unbiopsied embryos. There were no significant differences in regard to other obstetric and neonatal outcomes between the two groups.ConclusionsTrophectoderm biopsy is a safe approach, as the neonatal outcomes from biopsied and unbiopsied embryos were comparable. Furthermore, PGT is associated with higher risks of gestational hypertension and abnormal umbilical cord but may have a protective effect on PROM.

Blastocyst quality and perinatal outcomes of frozen-thawed single blastocyst transfer cycles.

ObjectiveTo investigate the effects of blastocyst quality and morphological grade on the perinatal outcomes in patients undergoing frozen-thawed single blastocyst transfer cycles.MethodsThis single-center retrospective cohort study included 2648 singleton neonates resulting from frozen-thawed single blastocyst transfers performed between January 2017 and September 2021. Multivariate logistic regression was performed to evaluate perinatal outcomes for their association with blastocyst quality and morphological parameters.ResultTransfer of a good-quality blastocyst in a frozen-thawed cycle was associated with a lower rate of preterm delivery (PTD, adjusted OR =0.7, 95% CI 0.5-0.9; P=0.020) and a higher likelihood of a male neonate (adjusted OR =1.2, 95%CI 1.0-1.5; P=0.048). Compared with grade C inner cell mass (ICM) blastocyst transfer, grade B ICM (adjusted OR =0.5, 95%CI 0.2-0.9; P=0.027) and grade A ICM (adjusted OR =0.6, 95%CI 0.3-1.5; P=0.290) blastocyst transfers were associated with a lower rate of PTD, which was more evident for grade B ICM. After adjusting for confounders, the likelihood of a male neonate (grade B TE, OR =1.2, 95%CI 1.0-1.5, P=0.037; grade A TE OR =1.9, 95%CI 1.3-28, P=0.002) increased with increasing trophectoderm (TE) quality. Compared with expansion stage 4, the likelihood of a male neonate was 1.5 times greater with transfer of a stage 6 blastocyst (OR =1.5, 95%CI 1.0-2.3; P=0.06), and the risk of small for gestational age (SGA) was greater with transfer of a stage 5 blastocyst (adjusted OR =3.5, 95%CI 1.5-8.0; P=0.004). The overall grading of the blastocyst, expansion stage, ICM grade, and TE grade were not associated with length at birth, birthweight, large for gestational age (LGA), or birth defects (all P>0.05).ConclusionsIn frozen-thawed single blastocyst transfer cycles, transfer of a good-quality blastocyst was associated with a lower rate of PTD and a greater likelihood of a male neonate. Transfer of grade B ICM blastocysts decreased the rate of PTD, and TE quality was positively correlated with the likelihood of a male neonate.

Cytoplasmic strings between ICM and mTE are a positive predictor of clinical pregnancy and live birth outcomes: A time-lapse study.

BackgroundElective single blastocyst transfer (eSBT) is considered to reduce the incidence of multiple pregnancy compared to double embryo transfer. Blastocyst selection is the key to achieving pregnancy. In the past, morphological assessment was the main criterion used to select blastocyst. Some important morphological parameters are considered to be clinically valuable, such as cytoplasmic strings traversing from the inner cell mass (ICM) and mural trophectoderm (mTE).MethodsIn this study, 1,267 elective frozen-thawed eSBT cycles cultured in a time-lapse culture system from January 2018 to May 2019 were included. Blastocysts were grouped into “present” and “absent” according to the appearance of cytoplasmic strings between ICM and mTE cells. The “present” group was further categorized according to the quantity of cytoplasmic strings between the ICM and mTE cells.ResultsA time-lapse analysis indicated that cytoplasmic strings between ICM and mTE were more visible among good quality blastocysts. Furthermore, blastocysts with cytoplasmic strings showed higher clinical pregnancy and live birth rates (P = 0.011 and 0.003), while no significant differences were observed in abortion rate and birth weight (P = 0.466 and 0.556).ConclusionsIn conclusion, although the results of previous studies about cytoplasmic strings have been controversial, the present time-lapse analysis provides evidence for the first time that cytoplasmic strings between ICM and mTE cells are a positive predictor of clinical pregnancy and live birth outcomes in elective frozen-thawed single blastocyst transfer cycles.

What is the best strategy for slowly developing blastocysts?

Day 5 fresh blastocyst transfers results in higher clinical pregnancy and live birth rates than day 6 fresh blastocyst transfer. This study aimed to identify the strategy to adopt with slowly developing blastocysts. Should not fully expanded blastocyst on day 5 be transferred on day 5, or when expanded on day 6, or be frozen? 1093 single blastocyst transfer cycles performed between January 2016 and December 2018 were divided in 4 groups: day 5 fresh transfers of full or expanded blastocyst (≥B3), day 5 fresh transfers of slowly developing blastocysts (B1 or B2), day 6 fresh transfers of expanded blastocysts (≥B4), day 6 frozen-thawed single blastocyst transfer cycles. Clinical pregnancy rate and live birth rate were significantly higher with fresh expanded blastocyst transfer on day 5 than in any other group. No statistical difference could be found between the other 3 groups. Slowly developing day 5 blastocysts have poorer implantation potential than expanded day 5 blastocysts but can be fresh transferred on day 5 rather than being cultured until day 6 for transfer or freezing when no expanded blastocyst is available on day 5.

Perinatal outcomes of singleton live births after preimplantation genetic testing during single frozen-thawed blastocyst transfer cycles: a propensity score-matched study

To determine whether singleton pregnancy achieved after preimplantation genetic testing (PGT) is associated with a higher risk of adverse perinatal outcomes than invitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) singleton pregnancy. A retrospective cohort study. A university-affiliated fertility center. This cohort study included singleton live births resulting from PGT (n = 232) and IVF/ICSI singleton pregnancies (n=2,829) with single frozen-thawed blastocyst transfer. Multiple baseline covariates were used for propensity score matching, yielding 214 PGT singleton pregnancies matched to 617 IVF/ICSI singleton pregnancies. Trophectoderm biopsy. The primary outcome was gestational hypertension, and various clinical perinatal secondary outcomes related to maternal and neonatal health were measured. Compared with IVF/ICSI singleton pregnancy, PGT singleton pregnancy was associated with a significantly higher risk of gestational hypertension (adjusted odds ratio, 2.58; 95% confidence interval, 1.32, 5.05). In the matched sample, the risk of gestational hypertension remained higher with PGT singleton pregnancy (odds ratio, 2.33; 95% confidence interval, 1.04, 5.22) than with IVF/ICSI singleton pregnancy. No statistical differences were noted in any other measured outcomes between the groups. The perinatal outcomes of PGT and IVF/ICSI singleton pregnancies were similar except for the observed potentially higher risk of gestational hypertension with PGT singleton pregnancy. However, because the data on PGT singleton pregnancies are limited, this conclusion warrants further investigation.

P–760 Cycle outcomes in frozen-thawed single blastocyst transfers in overweight and obese women

Abstract Study question Are cycle outcomes different in frozen embryo transfer in obese and overweight women compared to normal weight cases? Summary answer As BMI increases, although implantation rates are similar, miscarriage rates increase and live birth rates decrease, especially in cases whose BMI value is above 30. What is known already Obesity has adverse effects on the reproductive system. Obesity causes ovulatory dysfunction and menstrual cycle disorders, thus reducing fertility. As BMI increases, the implantation, pregnancy and ongoing pregnancy rates decrease and the rate of clinical losses increases. In donor oocyte cycles, the BMI of the recipient has a statistically significant detrimental effect on obstetrics outcomes such as pregnancy rate and live birth rate. However, very few studies evaluate the impact of BMI on frozen-thawed single blastocyst transfer. Study design, size, duration This retrospective study was conducted at Istanbul Memorial Hospital, ART and Reproductive Center between 2011 and 2020. A total of 5642 frozen-thawed single blastocyst transfer cycles were examined. Patients were grouped according to the World Health Organisation BMI classification system: Group I (BMI 25–29.9) (n = 1663); Group II (BMI 30–34.9) (n = 598); Group III (BMI 35–39.9) (n = 150); Group IV (BMI&amp;gt;40) (n = 30); Control Group (BMI 18.5–24.9) (n = 3201). Participants/materials, setting, methods: Patients between 17–42 years old were included. Preimplantation genetic diagnosis (PGD) was performed for patients &amp;gt;37 years old. Exclusion criteria were: repeated pregnancy losses, Mullerian abnormalities, intrauterine adhesions, endometrial thickness &amp;lt;7mm during frozen embryo transfer (FET) cycle. For endometrial preparation, modified natural cycle or artificial cycle were used. Single top/good quality blastocysts were transferred. Main results and the role of chance A total of 5642 FET cycles were analyzed. There was no significant difference in patient characteristics in terms of mean age, endometrial thickness on embryo transfer day and Anti Mullerian Hormone levels between the groups. Cycle outcomes were analysed according to the BMI groups. Mean age of groups were 32.1(17–42), 32(18–42), 32.6(20–42), 32.8(23–42) in groups I to IV respectively and 32(18–42) in the control group. Pregnancy rates were 70.9%(n = 1180) 70.7%(n = 423), 76%(n = 114) and 54.8%(n = 17) in groups I to IV respectively and 72.4% in the control group(n = 2321) (p &amp;gt; 0,05). Clinical pregnancy losses rates were 18.9%(n = 196), 23.9%(n = 86), 23.1%(n = 22) and 23%(n = 3) in groups I to IV respectively and 15.1% in the control group(n = 316) (p &amp;lt; 0,05). The live birth rates were 49.9%(n = 830) 45.1%(n = 270), 47.3%(n = 71) and 33.3%(n = 10) in groups I to IV, respectively and 54.9% (n = 1759) in the control group (p &amp;lt; 0,05). There was no statistically significant difference in implantation rates between the groups but clinical pregnancy losses rates were higher in obese patients (groups II-III-IV) whereas live birth rates were lower compared to group I (overweight) and the control group. Limitations, reasons for caution The limitation of the study is its retrospective nature. Wider implications of the findings: Our study shows that, there is a significantly higher risk of negative cycle outcomes in obese patients. Pre-treatment counselling is therefore needed to increase patient awareness of the risks and to provide advice on weight loss. Trial registration number Not applicable

P–772 Blastocyst quality and perinatal outcomes in women undergoing single blastocyst transfer in frozen cycles

Abstract Study question Is the morphological grading systems of a blastocyst associated with perinatal outcomes in women undergoing frozen-thawed single blastocyst transfer (SBT)? Summary answer Preferential transfer of a blastocyst based on their morphological grading systems appears to be supported by observed differences in perinatal outcomes. What is known already The transfer of a morphologically good quality blastocyst is associated with higher implantation and pregnancy rates as compared with a poor quality blastocyst. However to date, the association of the morphologic parameters of the blastocyst (developmental stage, inner cell mass (ICM), and trophectoderm (TE)) with the perinatal outcomes after blastocyst transfer remains unknown. Study design, size, duration A retrospective cohort study including 21,648 frozen-thawed SBT cycles from January 2013 to March 2019. Participants/materials, setting, methods 6037 women with singleton delivery in Peking University Third Hospital were eligible for analysis. Multivariate logistic regression was used to test the risk of factors with the expression of crude odds ratios (OR) and adjusted OR (aOR) with 95% confidence intervals (CI). Main results and the role of chance Transfer of a blastocyst with grading lower than 3BB was associated with a higher chance of female baby (49% vs 43%, aOR = 1.27 (1.12, 1.43)) and a higher rate of cesarian section (C-section) (69% vs 65%, aOR = 1.17 (1.03, 1.34)). Compared with stage 4 blastocyst, transfer of a stage 3 blastocyst was associated with a higher chance of preterm delivery (PTD) (aOR = 1.77 (1.08, 2.90)). Both stage 3 and stage 6 blastocyst transfer was associated with a lower chance of female baby (aOR = 0.68 (0.48, 0.97), 0.66 (0.47, 0.93), respectively). Compared with grade A ICM blastocyst transfer, Grade B ICM and grade C ICM blastocyst transfer was associated with a lower chance of a female baby (adjusted OR = 0.84 (0.73, 0.96), 0.63 (0.48, 0.83), respectively) and a higher risk of large for gestational age (LGA) (aOR = 1.20 (1.01, 1.42), 1.46 (1.07, 1.98), respectively). Grade C ICM blastocyst transfer was associated with an increased risk of macrosomia (aOR = 1.66 (1.14, 2.42)).Grade B TE and grade C TE blastocyst transfer had a lower risk of gestational diabetes mellitus (GDM) (aOR = 0.76 (0.60, 0.98), 0.69 (0.50, 0.94), respectively) than grade A TE blastocyst transfer. Limitations, reasons for caution The main limitations of this study were its retrospective nature and the relative subjectivity of blastocyst scoring. The follow-up was conducted through a phone call and some patients might not report their obstetrical and neonatal outcomes, leading to a relatively lower rate of several obstetrical outcomes. Wider implications of the findings: Transfer of a poor quality blastocyst is associated with a higher rate of C-section. The association between ICM grading and LGA and macrosomia would suggest that blastocysts with grade A ICM grading should be transferred preferentially and supports the use of current morphological grading systems for embryo prioritisation. Trial registration number N/A

Advanced trophectoderm quality increases the risk of a large for gestational age baby in single frozen-thawed blastocyst transfer cycles.

Does trophectoderm (TE) quality affect birthweight after single frozen-thawed blastocyst transfer? Transfer of single blastocyst with advanced TE quality was associated with higher birthweight and increased risk of a large for gestational age (LGA) baby. Transfer of blastocysts with advanced TE quality results in higher ongoing pregnancy rates and a lower miscarriage risk. However, data on the relationship between TE quality and birthweight are still lacking. This retrospective cohort study at a tertiary-care academic medical center included 1548 singleton babies born from single frozen-thawed blastocyst transfer from January 2011 to June 2019. Babies were grouped into four groups according to embryo expansion (Stages 3, 4, 5 and 6), three groups according to inner cell mass (ICM) quality (A, B and C), and three groups according to TE quality (A, B and C). Main outcomes included absolute birthweight, Z-scores adjusted for gestational age and gender, and adverse neonatal outcomes. Multivariable linear and logistic regression analyses were performed to investigate the association of neonatal outcomes with expansion stage, ICM quality and TE quality. As TE quality decreased, birthweight (3468.10 ± 471.52, 3357.69 ± 522.06, and 3288.79 ± 501.90 for A, B and C, respectively, P = 0.002), Z-scores (0.59 ± 1.07, 0.42 ± 1.04, and 0.27 ± 1.06 for A, B and C, respectively, P = 0.002) and incidence of LGA (28.9%, 19.7% and 17.4% for A, B and C, respectively, P = 0.027) decreased correspondingly. After adjusting for confounders, compared with the Grade A group, blastocysts with TE Grade B (standardized coefficients (β): -127.97 g, 95% CI: -234.46 to -21.47, P = 0.019) and blastocysts with TE grade C (β: -200.27 g, 95% CI: -320.69 to -79.86, P = 0.001) resulted in offspring with lower birthweight. Blastocysts with TE grade C brought babies with lower Z-scores than TE Grade A (β: -0.35, 95% CI: -0.59 to -0.10, P = 0.005). Also, embryos with TE Grade B (adjusted odds ratio (aOR):0.91, 95% CI: 0.84 to 0.99, P = 0.033) and embryos with TE Grade C (aOR : 0.89, 95% CI: 0.81 to 0.98, P = 0.016) had lower chance of leading to a LGA baby than those with TE Grade A. No association between neonatal outcomes with embryo expansion stage and ICM was observed (all P > 0.05). The retrospective design, lack of controlling for several unknown confounders, and inter-observer variation limited this study. The study extends our knowledge of the down-stream effect of TE quality on newborn birthweight and the risk of LGA. This study was funded by National Key R&D Program of China (2018YFC1003000), National Natural Science Foundation of China (81771533 to Y.P.K. and 31200825 to L.S.) and Innovative Research Team of High-level Local Universities in Shanghai (SSMU-ZLCX20180401), Shanghai Sailing Program(21YF1423200) and the Fundamental research program funding of Ninth People's Hospital affiliated to Shanghai Jiao Tong university School of Medicine (JYZZ117). The authors declare no conflict of interest in this present study. N/A.

Monozygotic dichorionic-diamniotic pregnancies following single frozen-thawed blastocyst transfer: a retrospective case series

BackgroundThe primary aim of the study is to report cases of monozygotic dichorionic-diamniotic (DC-DA) pregnancies after single frozen-thawed blastocyst transfer.MethodsThis is a retrospective case series. All single frozen-thawed blastocyst transfer cycles performed between June 2013 and December 2018 at the Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China, were reviewed retrospectively. We included frozen embryo transfer (FET) cycles which clinical pregnancy was confirmed with multiple gestational sacs showed on ultrasonography at around 6 to 7 weeks of gestation. We then conducted an in-depth analysis to further exclude cases which contained newborns of different genders or natural FET cycles.ResultsFive thousand four hundred fifteen frozen-thawed single blastocyst transfer cycles were preformed between June 2013 and December 2018 at the Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China. Of these, fourteen women underwent a single blastocyst transfer and then achieved clinical pregnancy with an ultrasound diagnosis of multi-chorionic pregnancy. With one natural cycle FET excluded, we finally included thirteen single blastocyst transfer cycles performed in down-regulated controlled FET or hormone replacement FET, in which the possibility of concurrently spontaneous pregnancy was extremely small. These included 13 cases reveal the phenomenon of monozygotic DC-DA twinning after single blastocyst transfer, which challenges the classical theory that only monochorionic pregnancy could happen after 3 days of fertilization.ConclusionThis case series suggest that single blastocyst transfer could result DC-DA pregnancies during IVF treatment.

Is there a critical LH level for hCG trigger after the detection of LH surge in modified natural frozen-thawed single blastocyst transfer cycles?

PurposeThere is no consensus yet in the literature on an optimal luteinizing hormone (LH) level for human chorionic gonadotrophin (hCG) trigger timing in patients undergoing frozen-thawed embryo transfer (FET) with modified natural cycles (mNC). The objective of our study was to compare the clinical results of hCG trigger at different LH levels in mNC-FET cases.MethodsThis retrospective study was conducted in Istanbul Memorial Hospital ART and Genetics Center. A total of 1076 cases with 1163 mNC-FET cycles were evaluated. LH levels between the start of LH rise (15 IU/L) and LH peak level (> 40 IU/L) were evaluated. Cycles were analyzed in four groups: group A (n = 287) LH level on the day prior to the day of hCG; groups B, C and D, LH levels on the day of hCG: group B (n = 245) LH 15–24.9; group C (n = 253), LH 25–39.9; group D (n = 383) LH ≥ 40. Cycle outcomes in the four groups were compared.ResultsSubgroup analyses of mNC-FET groups showed that implantation, clinical and ongoing pregnancy rates, and pregnancy losses were not significantly different in patients with different LH levels on the day of hCG trigger.ConclusionOur study suggests that hCG can be administered at any time between the start of LH rise (≥ 15 IU/L) and LH peak level (≥ 40 IU/L) without a detrimental effect on clinical outcome.

Delayed blastulation has no impact on neonatal outcomes in frozen-thawed single blastocyst transfer cycles

Delayed blastulation has no impact on neonatal outcomes in frozen-thawed single blastocyst transfer cycles

Transdermal versus oral estrogen: clinical outcomes in patients undergoing frozen-thawed single blastocyst transfer cycles without GnRHa suppression, a prospective randomized clinical trial

PurposeTo conduct a non-inferiority study to compare the clinical outcomes of transdermal estrogen patch and oral estrogen in patients undergoing frozen-thawed single blastocyst transfer non-donor cycles without GnRHagonist (GnRHa) suppression.MethodsA total of 317 women with irregular menses or anovulatory cycle undergoing frozen-thawed embryo transfer (FET) non-donor cycles without GnRHa suppression were involved in a prospective randomized clinical trial between May 2017 and October 2017. The trial was conducted in an ART and Reproductive Genetics Centre within a private hospital. The unit is designated as a teaching center by the Turkish Ministry of Health. Oral or transdermal estrogen was administered in patients undergoing frozen-thawed single blastocyst transfer. The outcomes of the study were the following: endometrial thickness on the day of progesterone administration, implantation rate, and clinical and viable ongoing pregnancy rates.ResultsEndometrial thickness and clinical outcomes of oral and transdermal estrogen administration were equally successful (p > 0.05).ConclusionNo significant difference was found in endometrial thickness on the day of progesterone administration nor in clinical outcomes between transdermal estrogen and oral estrogen in patients undergoing frozen-thawed single blastocyst stage transfer cycles without GnRHa suppression.

Noninvasive chromosome screening improves the clinical outcomes in frozen-thawed single blastocyst transfer cycles

To perform a clinical evaluation of the efficacy of single embryo transfer at blastocyst stage selected using the noninvasive chromosome screening (NICS) assay, which involves the sequencing of free genomic DNA in the culture medium of individual blastocysts for obtaining chromosomal ploidy information. A retrospective observational study from September 2015 to September 2016. A total of 353 frozen-thawed single blastocyst transfer (SBT) cycles were divided into three groups with different blastocyst selection criteria: the first was the No-choice group which had only one blastocyst for transfer for each patient (n=285). The second was the Morphology group. The patients of this group had at least two blastocysts available and blastocysts were selected for single blastocyst transfer on the basis of traditional morphological assessments (n=41); the third was the NICS group that had at least two blastocysts for each patient and the euploid blastocysts were selected using NICS for single blastocyst transfer (n=27). The biochemical pregnancy rate in the No-choice group, the Morphology group and the NICS group was 65.3%, 65.9% and 85.2%, respectively (P=0.232). Among three groups, the NICS group had the highest implantation rate (63.0%) (P=0.193), compared with 56.1% and 45.3% in the Morphology group and the No-choice group, respectively. There was no incidence of early miscarriage in the NICS group, while the early miscarriage rate in the No-choice group and the Morphology group was 21.1% and 13.0%, respectively (P=0.094). A significant difference was found in the ongoing pregnancy rate among the three groups, which was highest in the NICS group (63.0%) and lowest in the No-choice group (37.9%) (P=0.016). NICS is a novel genetic testing that allows an accurate selection of blastocysts with better developmental potential for transfer and might improve the clinical outcomes.