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Impact of Day 7 Blastocyst Transfer on Obstetric and Perinatal Outcome of Singletons Born After Vitrified-Warmed Embryo Transfer.

ABSTRACT: Background:Extended embryo culture has been reported to affect perinatal outcome regarding higher risks of large for gestational age (LGA) and preterm birth (PTB) yet decreased risk of small for gestational age (SGA). However, existing data about the obstetric outcome and the safety for offspring resulting from the transfer of day 7 blastocysts is rare. Objectives:To compare obstetric and perinatal outcome using embryos vitrified on day 7 with those vitrified on day 3, day 5, and day 6. Methods:Data were collected from 4489 infertile women who gave birth to live-born singletons after vitrified-warmed embryo transfer cycles from January 1, 2006 to December 31, 2017. Singletons were compared depending on the age of embryos. Main perinatal outcome parameters included PTB (gestational age < 37 weeks), very PTB (VPTB, gestational age < 32 weeks), LGA (birthweights > 90th percentiles), and SGA (birthweights < 10th percentiles). Obstetric outcomes included gestational diabetes (GDM), pregnancy-induced hypertension (PIH), preterm premature rupture of membranes (PPROM), pre-eclampsia, placenta previa, placental abruption, and postpartum hemorrhage. Propensity score matching (PSM) was used to adjust the confounding factors across groups and then analyze the association between in vitro culture period and the outcome measures. Results:After PSM, the transfer of day 7 blastocysts was associated with higher birth weight Z-scores and increased incidence of very large for gestational age (VLGA) compared with the transfer of day 3 cleavage-stage embryos while the incidence of PTB, low birth weight (LBW), SGA did not reach statistical significance. Moreover, comparable perinatal outcome was found in the comparison of day 7 vs. day 5 and day 7 vs. day 6. Day 7 blastocysts did not result in adverse obstetric outcome compared with day 3, day 5, and day 6 embryos, respectively. Conclusion:In vitrified-warmed transfer cycles, day 7 blastocysts were associated with adverse perinatal outcome regarding higher risk of VLGA compared with day 3 cleavage-stage embryo, while blastocysts with diverse growth rates embrace similar developmental viability regardless of blastocysts vitrified on day 5, day 6, or day 7.

SUBMITTER: Huang J

PROVIDER: S-EPMC7028682 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Impact of Day 7 Blastocyst Transfer on Obstetric and Perinatal Outcome of Singletons Born After Vitrified-Warmed Embryo Transfer.

Huang Jiaan J Yang Xiaoyan X Wu Jiayi J Kuang Yanping Y Wang Yun Y

Frontiers in physiology 20200212

<h4>Background</h4>Extended embryo culture has been reported to affect perinatal outcome regarding higher risks of large for gestational age (LGA) and preterm birth (PTB) yet decreased risk of small for gestational age (SGA). However, existing data about the obstetric outcome and the safety for offspring resulting from the transfer of day 7 blastocysts is rare.<h4>Objectives</h4>To compare obstetric and perinatal outcome using embryos vitrified on day 7 with those vitrified on day 3, day 5, and ...[more]

PMID: 32116782

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Project description:Background:Previous studies have reported the association between embryo quality and perinatal outcomes in fresh cycles, after cleavage-stage or blastocyst embryo transfer, and found no significant difference. However, in terms of vitrified-warmed embryo transfer cycles, the impact of embryo quality on neonatal and maternal outcomes has not been evaluated. Objectives:To explore the association between the quality of a single vitrified-warmed embryo and perinatal outcomes. Methods:This retrospective study included 2403 live-born singletons derived from single vitrified-warmed embryo transfer cycles during January 2006 and July 2018. Neonatal and maternal outcomes were compared between singletons resulting from the use of single good quality embryo (GQE) (n = 1854) and single poor quality embryo (PQE) (n = 549) and analyzed in the group of cleavage-stage embryo transfer and the group of blastocyst transfer, respectively. Results:A significantly higher risk of low birthweight (LBW, birthweight <2500 g) was observed in the singletons derived from the transfer of single PQE compared with those derived from the transfer of single GQE both in cleavage and blastocyst stages (cleavage-stage, AOR 2.62, 95% CI 1.27-5.37; blastocyst stage, AOR 1.98, 95% CI 1.06-3.70). An increased risk of preterm birth (PTB, gestational age <37 weeks) was also observed in singletons born after transfer of a PQE of cleavage-stage compared with those after a GQE of cleavage-stage (AOR 2.40, 95% CI 1.28-4.49). The transfer of single poor quality blastocyst was associated with a higher risk of placenta previa compared with the transfer of single good quality blastocyst (AOR 2.65, 95% CI 1.26-5.57). Other maternal complications, neonatal malformations, and neonatal complications were similar between compared groups. Conclusion:In vitrified-warmed cycles with single embryo transfer, poor embryo quality would result in a significantly higher risk of LBW, regardless of cleavage-stage or blastocyst embryo transfer. Meanwhile, the transfer of poor cleavage-stage embryo was also associated with an increased incidence of PTB.

Project description:The advent of assisted reproductive technologies (ART) in mammals involved an extraordinary change in the environment where the beginning of a new organism takes place. Under in vitro conditions, in which ART is currently being performed, it likely fails to mimic optimal in vivo conditions. This suboptimal environment could mediate in the natural developmental trajectory of the embryo, inducing lasting effects until later life stages that may be inherited by subsequent generations (transgenerational effects). Therefore, we evaluated the potential transgenerational effects of embryo exposure to the cryopreservation-transfer procedure in a rabbit model on the offspring phenotype, molecular physiology of the liver (transcriptome and metabolome) and reproductive performance during three generations (F1, F2 and F3). The results showed that, compared to naturally-conceived animals (NC group), progeny generated after embryo exposure to the cryopreservation-transfer procedure (VT group) exhibited lower body growth, which incurred lower adult body weight in the F1 (direct effects), F2 (intergenerational effects) and F3 (transgenerational effects) generations. Furthermore, VT animals showed intergenerational effects on heart weight and transgenerational effects on liver weight. The RNA-seq data of liver tissue revealed 642 differentially expressed transcripts (DETs) in VT animals from the F1 generation. Of those, 133 were inherited from the F2 and 120 from the F3 generation. Accordingly, 151, 190 and 159 differentially accumulated metabolites (DAMs) were detected from the F1, F2 and F3, respectively. Moreover, targeted metabolomics analysis demonstrated that transgenerational effects were mostly presented in the non-polar fraction. Functional analysis of molecular data suggests weakened zinc and fatty acid metabolism across the generations, associated with alterations in a complex molecular network affecting global hepatic metabolism that could be associated with the phenotype of VT animals. However, these VT animals showed proper reproductive performance, which verified a functional health status. In conclusion, our results establish the long-term transgenerational effects following a vitrified embryo transfer procedure. We showed that the VT phenotype could be the result of the manifestation of embryonic developmental plasticity in response to the stressful conditions during ART procedures.

Project description:BackgroundThe KIDScore™ Day 5 (KS-D5) model, version 3, is a general morphokinetic prediction model (Vitrolife, Sweden) for fetal heartbeat prediction after embryo transfer that was developed based on a large data set that included implantation results from a range of clinics with different patient populations, culture conditions and clinical practices. However, there was no study to comparing their pregnancy and live birth prediction ability among different maternal age. The aim of this study is to analyze the performance of KS-D5 in predicting pregnancy and live birth in various maternal age groups after single vitrified-warmed blastocyst transfer (SVBT).MethodsA total of 2486 single vitrified-warmed blastocyst transfer (SVBT) cycles were analyzed retrospectively. Confirmed fetal heartbeat positive (FHB+) and live birth (LB+) rates were stratified by Society for Assisted Reproductive Technology (SART) maternal age criteria (< 35, 35-37, 38-40, 41-42 and ≥ 43 years of age). Within each age group, the performance of the prediction model was calculated using the AUC, and the results were compared across the age groups.ResultsIn all age groups, the FHB+ rates decreased as the KIDScore decreased (P < 0.05). Conversely, the AUCs increased as the maternal age increased. The AUC of the < 35 age group (0.589) was significantly lower than the AUCs of the 41-42 age group (0.673) and the ≥43 age group (0.737), respectively (P < 0.05). In all age groups, the LB+ rates decreased as the KIDScore decreased (P < 0.05). Conversely, the AUCs increased as the maternal age increased. The AUC of the ≥43 age group (0.768) was significantly higher than the AUCs of other age groups (P < 0.05; < 35 age group = 0.596, 35-37 age group = 0.640, 38-40 age group = 0.646, 41-42 age group = 0.679).ConclusionsIn the present study, we determined that the KIDScore model worked well for prediction of pregnancy and live birth outcomes in advanced age patients.

Project description:Study questionIs supraphysiologic estradiol (E2) an independent predictor of low birth weight (LBW) in singletons born after fresh IVF-embryo transfer (ET) cycles?Summary answerOur results suggest that E2 > 2500 pg/ml is an independent predictor for LBW in full-term singletons born to normal responder patients undergoing fresh IVF-ET cycles.What is known alreadyThe pathogenesis of LBW in IVF singletons remains unknown. However, recent studies have suggested that the hyperestrogenic milieu generated during ovarian stimulation may create a sub-optimal peri-implantation environment, leading to placental dysfunction, and therefore, LBW.Study design, size, durationRetrospective cohort study of normal responder patients, <40 years old, undergoing fresh IVF-ET cycles resulting in live singleton births between January 2005 and June 2014.Participants/materials, setting, methodsA total of 6419 patients had live births after fresh IVF-ET during the study period, of which 2348 (36.6%) patients were excluded due to multiple gestation, vanishing twins or incomplete records. Perinatal outcomes recorded for all patients included birth weight, gestational age (GA) at delivery, mode of delivery and gender. Term birth, preterm birth (PTB) and LBW incidence proportions were plotted against E2 level on the day of trigger. The term LBW incidence proportion (i.e. singletons born at GA ? 37 weeks with birth weight <2500 g) was considered the primary outcome of interest.Main results and the role of chanceA total of 4071 patients with live singleton births were included. The median age, BMI, E2 level and birth weight for the study cohort was 36 (33-39) years, 22.3 (20.4-25.0) kg/m2, 1554 (1112.7-2179) pg/ml and 3289 (2920-3628) g, respectively. The incidence proportion of LBW rose from 6.4% (E2 2001-2500 pg/ml) to 20.7% (E2 3501-4000 pg/ml), without a corresponding rise in the incidence proportion of PTB. The odds of term LBW with E2 > 2500 pg/ml were 6.1-7.9 times higher compared to the referent E2 group. Multivariable logistic regression analysis revealed that E2 was an independent predictor for term LBW, even after adjusting for age, BMI, race, parity, infertility diagnosis, duration of ovarian stimulation, gonadotropin dosage and method of insemination (adjusted odds ratio 10.8, 95% CI 9.2-12.5). Receiver operating characteristic analysis generated an AUC estimate of 0.85 for E2 level as a predictor of LBW.Limitations reasons for cautionThe current study did not include analyses of hypertensive disorders of pregnancy or placental abnormalities. Furthermore, all patients were normal responders and of normal BMI, possibly limiting the overall generalizability of the study. Finally, as with any retrospective study, prospective data are required to validate the role of E2 in predicting LBW.Wider implications of the findingsOur results emphasize the importance of minimizing the supraphysiologic elevations of E2 levels during ovarian stimulation in fresh IVF-ET cycles. This, in turn, can optimize the early peri-implantation environment and mitigate adverse perinatal outcomes such as LBW.Study funding/competing interest(s)Dr Paul J. Christos was partially supported by the following grant: Clinical and Translational Science Center at Weill Cornell Medical College (UL1-TR000457-06).Trial registration numberN/A.

Dataset Information

Impact of Day 7 Blastocyst Transfer on Obstetric and Perinatal Outcome of Singletons Born After Vitrified-Warmed Embryo Transfer.

Publications

Impact of Day 7 Blastocyst Transfer on Obstetric and Perinatal Outcome of Singletons Born After Vitrified-Warmed Embryo Transfer.

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