Serum progesterone level above 0.85 ng/mL and progesterone/estradiol ratio may be useful predictors for replacing cleavage-stage with blastocyst-stage embryo transfer in fresh IVF/ICSI cycles without premature progesterone elevation

Author(s):  
Vehbi Yavuz Tokgoz ◽  
Ahmet Basar Tekin
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


Medicina ◽  
2019 ◽  
Vol 55 (6) ◽  
pp. 293 ◽  
Author(s):  
Kontopoulos ◽  
Simopoulou ◽  
Zervomanolakis ◽  
Prokopakis ◽  
Dimitropoulos ◽  
...  

Background and Objective: During the last few years, a trend has been noted towards embryos being transferred at the blastocyst stage, which has been associated with improved rates regarding implantation and clinical pregnancy in comparison to cleavage stage embryo transfers. There is a limited number of studies investigating this notion in oocyte donation cycles employing cryopreserved embryos. The aim of this study is to evaluate the implantation potential and clinical pregnancy rates between the day 3 cleavage stage and blastocyst stage embryo transfers in oocyte donation cycles employing vitrified embryos. Methods: This is a retrospective evaluation of oocyte donation frozen–thawed transfers completed in our clinic from January 2017 to December 2017. Intracytoplasmic sperm injection was conducted for all oocytes. Following fertilization, all embryos were cryopreserved either at the cleavage or blastocyst stage. Embryo transfer of two embryos was performed under direct sonographic guidance in all cases. Results: Our results confirmed a 55.6% clinical pregnancy (CP) resulting from day 3 embryo transfers, a 68.8% CP from day 5, and 71.4% CP from day 6. Significantly improved pregnancy rates were related to embryo transfers at the blastocyst stage when compared to cleavage stage transfers (68.9% and 55.6% respectively, p = 0.016). The risk with regards to multiple pregnancies was similar. Conclusion: Our findings indicate that in oocyte donation cycles employing vitrified embryos, embryo transfer at the blastocyst stage is accompanied with a significant improvement in pregnancy rates and merits further investigation.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
N Marconi ◽  
C Allen ◽  
S Bhattacharya ◽  
A Maheshwari

Abstract Study question Are obstetric/perinatal outcomes different in singleton pregnancies following blastocyst-stage embryo transfer when compared to cleavage-stage embryo transfer and have results changed over time? Summary answer Pregnancies following blastocyst are consistently associated with higher risk of large for gestational age and lower risk of small for gestational age babies What is known already Extended embryo culture to blastocyst-stage is widely used to select best embryos in in vitro fertilisation (IVF) cycles to improve pregnancy rates. Transfer of blastocyst-stage embryos is increasing with this being the default strategy in most clinics. As blastocysts are kept in culture until day 5, 6 or 7 after oocyte fertilisation, there are suggestions that longer exposure to culture media may have a negative impact on pregnancy outcomes. More recent primary studies have challenged some of the initial findings. We therefore conducted an updated systematic review and cumulative meta-analysis (CMA) to examine if these results have changed over time. Study design, size, duration Systematic review of studies published between 1980 and 2020, followed by aggregated meta-analysis and CMA to track the accumulation of evidence over the period of time. Exposed group: singleton pregnancies following blastocyst transfer. Non-exposed group: singleton pregnancies following cleavage-stage transfer. Sub-group analyses were conducted on fresh and frozen-thawed embryo transfers. Perinatal (categories of preterm birth and birth weight) and obstetric outcomes (hypertensive disorders of pregnancy, gestational diabetes, c-section, placental anomalies) were compared between the groups. Participants/materials, setting, methods Medline, EMBASE, CINHAL, Web of Science, Cochrane Central Register of Clinical Trials and International Clinical Trials Registry Platform databases were searched. Relevant journals were searched for advance access publications. Critical Appraisal Skills Programme (CASP) checklists were used to assess study quality. Two independent reviewers extracted data in 2 × 2 tables. Aggregated and CMA were performed using Comprehensive Meta-Analysis software. Risk ratio (RR) with 95% confidence interval (CI) were calculated. Main results and the role of chance A total of 33 observational studies were included (n = 574,756 singleton pregnancies). Pregnancies following blastocyst-stage embryo transfer are associated with a higher risk of preterm birth (PTB) (RR 1.09; 95% CI 1.01–1.17), very preterm birth (VPTB) (RR 1.15; 95% CI 1.07–1.24), large for gestational age (LGA) babies (RR 1.13; 95% CI 1.08–1.19), c-section (RR 1.05; 95% CI 1.02–1.09), and with a lower risk of small for gestational age (SGA) babies (RR 0.86; 95% CI 0.81–0.93) as compared to singleton pregnancies following cleavage-stage embryo transfer. These findings were maintained in both fresh and frozen-thawed sub-groups for LGA and SGA. PTB was not significantly different in both sub-group analyses. The risk of VPTB was higher after blastocyst-stage embryo transfer only in the sub-group analysis of fresh embryo transfers (RR 1.17; 95% CI 1.09–1.27) and that of c-section only in the frozen-thawed sub-group (RR 1.08; 95% CI 1.04–1.12). No other statistically significant differences for the other outcomes were noted. The CMA suggests that for SGA and LGA subsequent studies have increased the precision of the point estimate with no change in the direction or magnitude of the treatment effect since 2014. Limitations, reasons for caution This analysis was constrained by the intrinsic limitations of observational studies with some of them receiving a CASP score &lt; 10. Adjustment for confounders was not possible and a high degree of clinical and statistical heterogeneity was noted among studies. Wider implications of the findings: Blastocyst is associated with a higher risk of LGA and a lower risk of SGA with a stable body of evidence since 2014. We may need to revisit the default position of extending embryo culture and individualise care, until further high-quality data from individual-patient-data of large registries are available. Trial registration number Not applicable


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