Live birth rate and neonatal outcome following cleavage-stage embryo transfer versus blastocyst transfer using the freeze-all strategy

2019 ◽  
Vol 38 (6) ◽  
pp. 892-900 ◽  
Author(s):  
Qianqian Zhu ◽  
Jing Zhu ◽  
Yun Wang ◽  
Bian Wang ◽  
Ningling Wang ◽  
...  
2020 ◽  
Vol 28 (1) ◽  
pp. 43-51
Author(s):  
Michael Awadalla ◽  
Nicole Vestal ◽  
Lynda McGinnis ◽  
Ali Ahmady

AbstractAccurate knowledge of the live birth rate for cleavage stage embryos is essential to determine an appropriate number of embryos to transfer at once. Results from previous studies lack details needed for practical use. This is a mathematical analysis and model building study of day 3 cleavage stage embryo transfers. A total of 996 embryos were transferred in 274 fresh and 83 frozen embryo transfers. Embryo morphology was divided into 4 groups based on number of cells and fragmentation percentage. Each embryo transfer was modeled as an equation equating the sum of the live birth rates of the transferred embryos to the number of live births that resulted. The least squares solution to the system of embryo transfer equations was determined using linear algebra. This analysis was repeated for ages 35 to 42 years old at oocyte retrieval. The best fit live birth rates per embryo in the age group centered on 35 years old were 29%, 13%, 10%, and 9% for embryos in the 8-cell with ≤ 5% fragmentation, 8-cell with > 5% fragmentation, 9–12 cell, and 6–7 cell groups, respectively. Cleavage stage embryos with fewer than 6 cells on day 3 had very low best fit live birth rates close to 0% at age 39 years and were excluded from the primary analysis to prevent overfitting. These live birth rates can be used with a simple embryo transfer model to predict rates of single and multiple gestation prior to a planned cleavage stage embryo transfer.


2020 ◽  
Vol 35 (10) ◽  
pp. 2365-2374
Author(s):  
N J Cameron ◽  
S Bhattacharya ◽  
D J McLernon

Abstract STUDY QUESTION Is there a difference in the odds of a live birth following blastocyst- versus cleavage-stage embryo transfer in the first complete cycle of IVF? SUMMARY ANSWER After adjusting for indication bias, there was not enough evidence to suggest a difference in the odds of live birth following blastocyst- versus cleavage-stage embryo transfer in the first complete cycle of IVF. WHAT IS KNOWN ALREADY Replacement of blastocyst-stage embryos has become the dominant practice in IVF but there is uncertainty about whether this technique offers an improved chance of cumulative live birth over all fresh and frozen-thawed embryo transfer attempts associated with a single oocyte retrieval. STUDY DESIGN, SIZE, DURATION National population-based retrospective cohort study of 100 610 couples who began their first IVF/ICSI treatment at a licenced UK clinic between 1 January 1999 and 30 July 2010. PARTICIPANTS/MATERIALS, SETTING, METHODS Data from the Human Fertilisation and Embryology Authority (HFEA) register on IVF/ICSI treatments using autologous gametes between 1999 and 2010 were analysed. The primary outcome was the live birth rate over the first complete cycle of IVF. Cumulative live birth rates (CLBR) were compared for couples who underwent blastocyst and cleavage transfer, and the adjusted odds of live birth over the first complete cycle were estimated for each group using binary logistic regression. This analysis was repeated within groups of female age, oocytes collected and primary versus secondary infertility. Inverse probability of treatment weighting was used to account for the imbalance in couple characteristics between treatment groups. MAIN RESULTS AND THE ROLE OF CHANCE In total, 94 294 (93.7%) couples had a cleavage-stage embryo transfer while 6316 (6.3%) received blastocysts. Over the first complete cycle of IVF/ICSI (incorporating all fresh and frozen-thawed embryo transfers associated with the first oocyte retrieval), the CLBR was increased in those who underwent blastocyst transfer (56.5%) compared to cleavage-stage embryo transfer (34.8%). However, after accounting for the imbalance between exposures, blastocyst transfer did not significantly influence the odds of live birth over the first complete cycle (adjusted odds ratio: 1.03 (0.96, 1.10)). LIMITATIONS, REASONS FOR CAUTION Limitations of our study include the retrospective nature of the HFEA dataset and availability of linked data up until 2010. We were unable to adjust for some confounders, such as smoking status, BMI and embryo quality, as these data are not collected at national level by the HFEA. Similarly, there may be unknown couple, treatment or clinic variables that may influence our results. We were unable to assess the intended stage of embryo transfer for women who did not have an embryo replaced, and therefore excluded them from our study. Perinatal outcomes were not included in our analyses and would be a useful basis for future study. WIDER IMPLICATIONS OF THE FINDINGS Our findings show that blastocyst-stage embryo transfer may offer an improved chance of live birth in both the first fresh and the first complete cycle of IVF/ICSI compared to cleavage-stage transfer, even in couples with typically poorer prognoses. Where possible, offering blastocyst transfer to a wider range of couples may increase cumulative success rates. STUDY FUNDING/COMPETING INTEREST(S) N.J.C. received a Wolfson Foundation Intercalated Degree Research Fellowship funded by the Wolfson Foundation, through the Royal College of Physicians. This work was supported by a Chief Scientist Office Postdoctoral Training Fellowship in Health Services Research and Health of the Public Research (Ref PDF/12/06) held by D.J.M. The views expressed here are those of the authors and not necessarily those of the Chief Scientist Office or the Wolfson Foundation. The funders did not have any role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; nor in the decision to submit the paper for publication. None of the authors has any conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A


2020 ◽  
Vol 27 (12) ◽  
pp. 2271-2278
Author(s):  
Xiaoyu Long ◽  
Yuanyuan Wang ◽  
Fangrong Wu ◽  
Rong Li ◽  
Lixue Chen ◽  
...  

Abstract This study aims to evaluate the effect of blastocyst- and cleavage-stage embryo transfers with different numbers of transferred embryos on pregnancy outcomes in China. This was a retrospective cohort study that collected 24,422 frozen-thawed embryo transfer (FET) cycles in two affiliated hospitals of Peking University Health Science Center between January 2015 and May 2018. They were divided into four groups: the single cleavage-stage embryo transfer group (C-1) (763 cycles), double cleavage-stage embryo transfer group (C-2) (13,004 cycles), single blastocyst-stage embryo transfer group (B-1) (7913 cycles), and double blastocyst-stage embryo transfer group (B-2) (2046 cycles). Of the four groups, the live birth rate was the lowest in the C-1 group (11.8%) while it was the highest in the B-2 group (33.6%). However, the B-2 group was accompanied with higher risks of miscarriages, maternal complications, twin births, preterm births, and low birth weight. Compared with the C-2 group, the B-1 group had a lower live birth rate (23.0 vs 29.0%; aOR, 0.78; 95% CI, 0.72–0.85), but also had a lower risk for twin births (1.9 vs 23.4%; aOR, 0.06; 95% CI, 0.04–0.09) and preterm births (9.6 vs 16.1%; aOR, 0.51; 95% CI, 0.41–0.65). The probability of live birth in the B-1 group declined from 0.25 at 20–29 years old to 0.08 at > 40 years old, while the probabilities of adverse outcomes went up with maternal age. It can be concluded that single-blastocyst embryo transfer seems to be the best choice for all maternal ages. This group of embryo transfer has significantly reduced adverse neonatal outcomes. Especially, women with younger maternal age in this group appear to prominently benefit from single-blastocyst transfer.


BMJ Open ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. e042395
Author(s):  
Simone Cornelisse ◽  
Liliana Ramos ◽  
Brigitte Arends ◽  
Janneke J Brink-van der Vlugt ◽  
Jan Peter de Bruin ◽  
...  

IntroductionIn vitro fertilisation (IVF) has evolved as an intervention of choice to help couples with infertility to conceive. In the last decade, a strategy change in the day of embryo transfer has been developed. Many IVF centres choose nowadays to transfer at later stages of embryo development, for example, transferring embryos at blastocyst stage instead of cleavage stage. However, it still is not known which embryo transfer policy in IVF is more efficient in terms of cumulative live birth rate (cLBR), following a fresh and the subsequent frozen–thawed transfers after one oocyte retrieval. Furthermore, studies reporting on obstetric and neonatal outcomes from both transfer policies are limited.Methods and analysisWe have set up a multicentre randomised superiority trial in the Netherlands, named the Three or Fivetrial. We plan to include 1200 women with an indication for IVF with at least four embryos available on day 2 after the oocyte retrieval. Women are randomly allocated to either (1) control group: embryo transfer on day 3 and cryopreservation of supernumerary good-quality embryos on day 3 or 4, or (2) intervention group: embryo transfer on day 5 and cryopreservation of supernumerary good-quality embryos on day 5 or 6. The primary outcome is the cLBR per oocyte retrieval. Secondary outcomes include LBR following fresh transfer, multiple pregnancy rate and time until pregnancy leading a live birth. We will also assess the obstetric and neonatal outcomes, costs and patients’ treatment burden.Ethics and disseminationThe study protocol has been approved by the Central Committee on Research involving Human Subjects in the Netherlands in June 2018 (CCMO NL 64060.000.18). The results of this trial will be submitted for publication in international peer-reviewed and in open access journals.Trial registration numberNetherlands Trial Register (NL 6857).


2019 ◽  
Vol 34 (9) ◽  
pp. 1716-1725 ◽  
Author(s):  
Nicola Marconi ◽  
Edwin Amalraj Raja ◽  
Siladitya Bhattacharya ◽  
Abha Maheshwari

Abstract STUDY QUESTION Are perinatal outcomes different between singleton live births conceived from fresh blastocyst transfer and those following the transfer of fresh cleavage-stage embryos? SUMMARY ANSWER Fresh blastocyst transfer does not increase risks of preterm birth (PTB), low/high birth weight or congenital anomaly and does not alter the sex ratio at birth or prejudice the chance of having a healthy baby. WHAT IS KNOWN ALREADY Extended embryo culture is currently considered the best option for embryo selection, but concerns have been raised about increased risks of preterm delivery and large-for-gestational-age (LGA) babies. STUDY DESIGN, SIZE, DURATION We conducted a retrospective cohort study based on data from the Human Fertilisation and Embryology Authority (HFEA) anonymised and cycle-based dataset in the UK between 1999 and 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS Baseline characteristics were compared between in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) blastocyst-stage and cleavage-stage embryo transfer cycles using the χ2 test for categorical/dichotomised covariates and the Mann–Whitney test for continuous covariates. Statistical significance was set at <0.005. Poisson regression and multinomial logistic regression were used to establish relationships between perinatal outcomes and blastocyst-stage embryo transfer or cleavage-stage embryo transfer. Risk ratios (RRs), adjusted risk ratios (aRRs) and their 99.5% confidence intervals (CIs) were calculated as a measure of strength of associations. Results were adjusted for clinically relevant covariates. A sub-group analysis included women undergoing their first IVF/ICSI treatment. The level of significance was set at <0.05, and 95% CIs were calculated in the sub-group analysis. MAIN RESULTS AND THE ROLE OF CHANCE Of a total of 67 147 IVF/ICSI cycles, 11 152 involved blastocyst-stage embryo(s) and 55 995 involved cleavage-stage embryo(s). The two groups were comparable with regards to the risk of PTB (aRR, 1.00; 99.5% CI, 0.79–1.25), very-preterm birth (VPTB) (aRR, 1.00; 99.5% CI, 0.63–1.54), very-low birth weight (VLBW) (aRR, 0.84; 99.5% CI, 0.53–1.34), low birth weight (LBW) (aRR, 0.92; 99.5% CI, 0.73–1.16), high birth weight (HBW) (aRR, 0.94; 99.5% CI, 0.75–1.18) and very-high birth weight (VHBW) (aRR, 1.05; 99.5% CI, 0.66–1.65). The risk of congenital anomaly was 16% higher in the blastocyst-stage group than in the cleavage-stage group, but this was not statistically significant (aRR, 1.16; 99.5% CI, 0.90–1.49). The chance of having a healthy baby (born at term, with a normal birth weight and no congenital anomalies) was not altered by extended culture (aRR, 1.00; 99.5% CI, 0.93–1.07). Extended culture was associated with a marginal increase in the chance having a male baby in the main cycle-based analysis (aRR, 1.04; 99.5% CI, 1.01–1.09) but not in the sub-group analysis of women undergoing their first cycle of treatment (aRR, 1.04; 95% CI, 1.00–1.08). In the sub-group analysis, the risk of congenital anomalies was significantly higher after blastocyst-stage embryo transfer (aRR, 1.42; 95% CI, 1.12–1.81). LIMITATIONS, REASONS FOR CAUTION This study is limited by the use of observational data and inability to adjust for key confounders, such as maternal smoking status and body mass index (BMI), which were not recorded in the HFEA dataset. As the main analysis was cycle-based and we were unable to link cycles within women undergoing more than one IVF/ICSI cycle, we undertook a sub-group analysis on women undergoing their first treatment cycle. WIDER IMPLICATIONS OF THE FINDINGS Our findings should reassure women undergoing blastocyst-stage embryo transfer. For the first time, we have shown that babies born after blastocyst transfer have a similar chance of being healthy as those born after cleavage-stage embryos transfer. STUDY FUNDING/COMPETING INTEREST(S) The research activity of Dr Nicola Marconi was funded by the scholarship ‘A. Griffini-J. Miglierina’, Fondazione Comunitaria del Varesotto, Provincia di Varese, Italy. The authors do not have any competing interests to disclose. TRIAL REGISTRATION NUMBER N/A


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